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Recessive oncogenes: Current status

  • Review
  • Published:
Pathology & Oncology Research

Abstract

Cell growth is under the control of a variety of positive and negative signals. An imbalance of such signals results in deregulation of cell behavior. Recessive oncogenes or tumor suppressor genes, opposite to dominant oncogenes, encode important cellular proteins which could function as negative regulators of the cell cycle, i.e., cell cycle brakes. Inactivation of recessive oncogenes, by allelic deletion, loss of expression, mutation, or functional inactivation by interacting with oncogene products of DNA tumor viruses or with amplified cellular binding proteins, will lead to uncontrolled cell growth or tumor formation. Besides the classic suppressor genes such as the p53 and RB, a growing number of novel tumor suppressor genes have been identified in recent years. While some tumor suppressor genes have been found to be important for the development of a large number of human malignancies (e.g., the p53 gene), others are more tumor type-specific (e.g., the NF-1 gene). Many human cancer types showed abnormalities of multiple tumor suppressor genes, offering strong support to the concept that tumorigenesis and progression result from an accumulation of multiple genetic alterations. In this review, we will begin with an overview (gene, transcript, protein and mechanisms of action) of the tumor suppressor genes (the RB, p53, DCC, APC, MCC, WT1, VHL, MST1, and BRCA1 genes) identified to date and then discuss the specific involvement of tumor suppressor genes in human malignancies including prostate cancer. Various chromosomal regions which potentially may contain tumor suppressor genes also will be reviewed.

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References

  1. Bishop JM: Molecular themes in oncogenesis. Cell 64: 235–248, 1991.

    Article  PubMed  CAS  Google Scholar 

  2. Hunter T: Cooperation between oncogenes. Cell 64: 249–270, 1991.

    Article  PubMed  CAS  Google Scholar 

  3. Marshall CJ: Tumor suppressor genes. Cell 64: 313–326, 1991.

    Article  PubMed  CAS  Google Scholar 

  4. Weinberg RA: Tumor suppressor gene. Science 254, 1138–1146, 1991.

    Article  PubMed  CAS  Google Scholar 

  5. Knudson AG: Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68: 820–823, 1971.

    Article  PubMed  Google Scholar 

  6. James CD, Carlvom E, Nordenskhold M, Mollins VP and Cavanee WK: Mitotic reconbination of chromosome 17 in astrocytomas. Proc Natl Acad Sci USA 86, 2858–2862, 1989.

    Article  PubMed  CAS  Google Scholar 

  7. Hollstein M, Sidransky D, Vogelstein B and Harris C: p53 mutations in human cancers, Science 253, 49–53, 1991.

    Article  PubMed  CAS  Google Scholar 

  8. Miki Y, Swensen J, Shattuck-Fidens K, Futreal PA, Harsh-man K, Tavtigian K, Liu Q, Cochran C, Bennett M, Ding W, Bell R, Rosenhhal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Wark J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A and Skoinick MH: A strong candidate for the breast and ovarian cancer susceptibility gene BRCAI. Science 266: 66–71, 1994.

    Article  PubMed  CAS  Google Scholar 

  9. Raychaudhuri P, Bagchi S, Devoto SH, Kraus, VB, Moran E and Nevins, JR: Domains of the adenovirus EIA protein required for oncogenic activity are also required for dissociation of E2F transcription factor complexes. Gene Devel 5: 1200–11, 1991.

    Article  CAS  Google Scholar 

  10. Slebos RJC, Lee MH, Plunkett BS, Kessis TD, Williams BO, Jacks T, Hedrick L, Kastan MB and Cho KR p53-dependent GI arrest involves pRB-related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein. Proc Natl Acad Sci USA, 91: 5320–5324, 1994.

    Article  PubMed  CAS  Google Scholar 

  11. Green MR: When the products of oncogenes and anti-onco-genes meet. Cell 56: 1–3, 1989.

    Article  PubMed  CAS  Google Scholar 

  12. Dalton S: Cell cycle regulation of the human cdc2 gene. EMBOJ, 11: 1797–804, 1992.

    CAS  Google Scholar 

  13. Nevins JR: Transcriptional regulation. A closer look at E2F. Nature 358: 375–6, 1992.

    Article  PubMed  CAS  Google Scholar 

  14. Eileen W: p53. guardian of Rb. Nature 371, 21–22, 1994.

    Article  Google Scholar 

  15. Weintraub SJ, Prater CA and Dean DC: Retinoblastoma protein switches the E2F site from positive to negative element. Nature 358: 259–61, 1992.

    Article  PubMed  CAS  Google Scholar 

  16. Peter M and Herskowitz I: Joining the complex: cyclindependent kinase inhibitory proteins and the cell cycle. Cell 79: 181–184, 1994.

    Article  PubMed  CAS  Google Scholar 

  17. Guan KL, Jenkins CW, Li Y, Nichols MA, Wu XY, Okeefe CL, Matera AG and Xiong Y: Growth suppresion by p18. a p16(INK4B/MTS1)-related and pl4(lNK4B/MTS2)-related CDK6 inhibityor, correlaes with wild-type pRB functions. Gene Develop 8: 2939–2952, 1994.

    Article  CAS  Google Scholar 

  18. Johnson DG, Schwarz JK, Cress WD and Nevins JR: Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature 365, 349–352, 1993.

    Article  PubMed  CAS  Google Scholar 

  19. Bookstein R and Allred DC: Recessive oncogenes. Cancer 71: 1179–1186, 1993.

    Article  PubMed  CAS  Google Scholar 

  20. Goodrich DW and Lee W-H: Molecular characterization of the retinoblastoma susceptibility gene. Bioch Biophys Acta 1155: 43–61, 1993.

    CAS  Google Scholar 

  21. Bookstein R, Shew J-Y, Chen P-L, Scully P, Lee WH: Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247: 712–715, 1990.

    Article  PubMed  CAS  Google Scholar 

  22. Bookstein R, Rio P, Madreperla S: Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc Natl Acad Sci USA, 87: 7762–7766, 1990.

    Article  PubMed  CAS  Google Scholar 

  23. Sarkar FH, Sakr W, Li Y-W: Analysis of retinoblastoma (RB) gene deletion in human prostatic carcinomas. Prostate 21: 145–152, 1992.

    Article  PubMed  CAS  Google Scholar 

  24. Phillips SMA, Morton DG, Lee SJ, Wallace DMA and Neoptolemos JP: Loss of heterozygosity of the retinoblastoma and adenomatous polyposis succeptibility gene loci and in chromosomes 10p, 10q and 16q in human prostate cancer. Brit J Urol 73: 390–395, 1994.

    Article  PubMed  CAS  Google Scholar 

  25. Carter BS, Ewing CM, Ward WS, Treiger BF, Aalders TW, Schalken JA, Epstein JI and Isaacs WB: Allelic loss of chromosomes 16q and 10q in human prostate cancer. Proc Natl Acad Sci USA 87: 8751–8755, 1990.

    Article  PubMed  CAS  Google Scholar 

  26. Levine AJ: The tumor suppressor genes. Annu Rev Biochem 62: 623–51, 1993.

    Article  PubMed  CAS  Google Scholar 

  27. Perry ME and Levine AJH: Tumor-suppressor p53 and the cell cycle. Curr Opin Genet Rev 3: 50–54, 1993.

    Article  CAS  Google Scholar 

  28. Demers GW, Foster SA, Halbert CL and Galloway DA: Growth arrest by induction of p53 in DNA damaged kera-tinocytes in bypassed by human papillomavirus 16E7. Proc Natl Acad Sci USA 91: 4382–4386, 1994.

    Article  PubMed  CAS  Google Scholar 

  29. Ryan JJ, Danish R, Bottilieb CA and Clarke ME: Cell cycle analysis of p53-induce cell death in murine erythroleukemia cells. Mol Cell Biol 13: 711–719, 1993.

    PubMed  CAS  Google Scholar 

  30. Hermeking H and Eick D: Mediation c-Myc-induced apoptosis by p53. Science 265: 2091–2093, 1994.

    Article  PubMed  CAS  Google Scholar 

  31. Vogelstein B and Kinzler KW: p53 function and dysfunction. Cell 70: 523–526, 1992.

    Article  PubMed  CAS  Google Scholar 

  32. Harris CC: p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981, 1993.

    Article  PubMed  CAS  Google Scholar 

  33. Mack DH, Vartikar J, Pipas JM and Laimins LA: Specific repression of TATA-mediated but not initiator-mediated transcritpion by wild-type p53, Nature 363: 281–283, 1993.

    Article  PubMed  CAS  Google Scholar 

  34. Duan L, Ozaki I., Oakes JW, Taylor JP, Khalili K and Pomerantz RJ: The tumor suppressor protein p53 strongly alters human immunodeficiency virus type 1 replication. J Virol 68: 4302–4313, 1994.

    PubMed  CAS  Google Scholar 

  35. Truant R, Xiao H, Ingles CJ and Greenblatt J: Direct interaction between the transcriptional activation domain of human p53 and the TATA box-binding protein. J Biol Chem 268: 2284–2287, 1993.

    PubMed  CAS  Google Scholar 

  36. Ragimov N, Krauskopf A, Navot N: Wild-type but not mutant can repress transcription initiation in vitro by interfering with the binding of basal transcription factors to the TATA motif. Oncogene 8: 1183–1193, 1993.

    PubMed  CAS  Google Scholar 

  37. Martin DW, Munoz RM, Subler MA and Deb S: p53 binds to the TATA-binding protein-TATA complex. J Biol Chem 268: 13062–13067, 1993.

    PubMed  CAS  Google Scholar 

  38. Liu X, Niller CW, Koeffler PH and Berk AJ: The p53 activation domain binds the TATA box-binding polypeptide in holo TFIID, and a neighboring p53 domain inhibits transcription. Mol Cell Biol 13: 3291–3300, 1993.

    PubMed  CAS  Google Scholar 

  39. EI-Deiry WS, Dern SE, Pietenpol JA, Kinder DW and Vogelstein B: Definition of a consensus binding site for p53. Nat Genet 45–49, 1992.

  40. Farmer G, Bargonettim J, Zhu H, Friedman P, Prywers R and Prives C: Wild-type p53 activates transcription in vitro. Nature 358: 83–86, 1992.

    Article  PubMed  CAS  Google Scholar 

  41. Wu X, Bayle JH, Olson D and Levine AJ: The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7: 1126–1132, 1993.

    Article  PubMed  CAS  Google Scholar 

  42. Zauberman A, Barak Y, Ragimov N, Levy N and Oren M: Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53-MDM2 complexes. EMBO J 12: 2799–2808, 1993.

    PubMed  CAS  Google Scholar 

  43. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer E, Kinzler DW and Vogelstein B: WAFI, a potential mediator of p53 tumor suppression. Cell 75: 817–825, 1993.

    Article  PubMed  CAS  Google Scholar 

  44. Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interaction protein Cipl is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805–16, 1993.

    Article  PubMed  CAS  Google Scholar 

  45. Miyashita T and Reed JC: Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293–299, 1995.

    Article  PubMed  CAS  Google Scholar 

  46. Chen YQ, Gao X, Grignon D, Sarkr FH, Sakr W, Honn KV, Borders JS and Crissman JD: Multiple mechanisms of p53 inactivation in human prostate cancer. Cancer Mol Biol 1: 357–367, 1994.

    CAS  Google Scholar 

  47. Kuerbitz SJ, Phunkett BS, Walsh WV and Kastan MB: Wildtype p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89: 7491–7495, 1992.

    Article  PubMed  CAS  Google Scholar 

  48. Gu Z, Pim D, Labrecque S, Banks L and Matlashewski G: DNA damage induced p53 mediated transcription is inhibited by human papillomavirus type 18 E6. Oncogene 9: 629–633, 1994.

    PubMed  CAS  Google Scholar 

  49. Lu X and Lane DP: Differential induction of transcriptionally active p53 following UV or lonizing radiation: defects in chromosome instability syndromes. Cell 75: 765–778, 1993.

    Article  PubMed  CAS  Google Scholar 

  50. White E: p53, guardian of Rb. Nature 371: 21–22, 1994.

    Article  PubMed  CAS  Google Scholar 

  51. Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CAJr, Butel JS and Bradley A: Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356: 215–21, 1992.

    Article  PubMed  CAS  Google Scholar 

  52. Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R and Beach D: p21 is a universal inhibitor of cyclin kinases. Nature 366: 701–704, 1993.

    Article  PubMed  CAS  Google Scholar 

  53. Malkin D, Li FP, Strong LC, Fraumeni JFF, Nelson CEJr, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA and Friend SH: Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250: 1233–1238, 1990.

    Article  PubMed  CAS  Google Scholar 

  54. Greenblatt MS, Bennett WP, Hollstein M and Harris CC: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878, 1994.

    PubMed  CAS  Google Scholar 

  55. Aguilar F, Hussain SP and Cerutti P: Aflatoxin Bl induces the transversion of G-T in codon 249 of the p53 tumor suppressor gene in human hepatocytes. Proc Natl Acad Sci USA 90: 8586–8590, 1993.

    Article  PubMed  CAS  Google Scholar 

  56. Leach FS, Taino T, Meltzer P, Burrell M, Oliner JD, Smith S, Hill DE, Sidransky D, Kinzler KW and Vogelstein B: p53 mutation and MDM2 amplification in human sotft tissue sarcomas. Cancer Res 53: 2231–2234, 1993.

    PubMed  CAS  Google Scholar 

  57. van Meir EG, Kikuchi T, Tuda M, Li H, Deserens A-C, Wijcik B E, Huang J-JS, Friedmann T, de Tribolet N and Caenee WK: Analysis of the p53 gene and its expression in human glioblastoma cells. Cancer Res 54: 649–652, 1994.

    PubMed  Google Scholar 

  58. Cordon-Cardo, C, Lotres, E, Drobnjak, M, Oliva, M R, Pollack, D, Woodruff, J M, Marchal. V, Chen, J, Broman, M F, and Levine, A J: Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res 54: 794–799, 1994.

    PubMed  CAS  Google Scholar 

  59. Eyfjord JE, Thorlacius S, Steinarsdottir M, Valgardsdottir R, Ogmundsdottir HM and Anamthawat-Jonsson K: p53 abnormalities and genomic instability in primary human breast carcinomas. Cancer Res 55: 646–651, 1995.

    PubMed  CAS  Google Scholar 

  60. Field JK, Malliri A, Jones AJ and Spandidos DA: Mutations in the p53 gene at codon 249 are rare in squamous cell carcinoma of the head and neck. Intl J Oncol 1: 253–256, 1992.

    CAS  Google Scholar 

  61. Kalthoff H, Schmiege E, Roeder C, Kasche D, Schmidt A, Lauer C, Thiele HG, Honold G, Pantel Riethmuller G, Scherer E, Maurer J, Maacke H Deppert W: p53 and K-RAS alteration in pancreatic epithelial cell lesions. Oncogene 8: 289–298, 1993.

    PubMed  CAS  Google Scholar 

  62. Renault B, Brock MVD, Fodde R, Wijnen J, Pellegata NS, Amadori D, Khan PM and Ranzani GN: Base transitions are the most frequent genetic changes at p53 in gastric cancer. Cancer Res 53: 2614–2617, 1993.

    PubMed  CAS  Google Scholar 

  63. Wei YD, Jiafu Z, Xi Q S, Yongjinag M, Xiulong Z, Daizong L and Jianren G: p53 gene mutations in Chinese human testicular seminoma. J Urol 150: 884–886, 1993.

    Google Scholar 

  64. Suzuki Y and Tamura G: Mutations of the p53 gene in carcinomas of the urinary system. Acta Pathol Japonica 43: 745–750, 1993.

    CAS  Google Scholar 

  65. Isaacs WB, Carter BS and Ewing CM: Wild-type p53 suppresses growth of human prostate cancer cells containing mutant p53 alleles. Cancer Res 51: 4716–4720, 1991.

    PubMed  CAS  Google Scholar 

  66. Gao X, Porter AT and Honn KV: Tumor suppressor genes and their involvement in human prostate cancer. Cancer Mol Biol 1995 (In press).

  67. Gao X and Honn KV: 12-lipoxygenase as a prostate cancer marker and therapeutic target. Adv Oncol 11: 3–9, 1995.

    Google Scholar 

  68. Meyers FJ, Chi S-G and Fishman JR: p53 mutations in benign prosatic hyperplasia. J. Natl Cancer Inst 85: 1856–1858, 1993.

    Article  PubMed  CAS  Google Scholar 

  69. Chi S-G, de Vere White RW, Meyers FJ, Siders DB, Lee F and Gumerlock PH: p53 in prostate cancer: Frequent expressed transition mutations. J. Natl Cancer Inst 86: 926–933, 1994.

    Article  PubMed  CAS  Google Scholar 

  70. Fearon ER, Cho KR, Nigro JM, Kern SE, Simons JW, Ruppert JM, Hamilton SR, Preisinger AC, Thomas G, Kinzler KW and Vogelstein B: Identification of a chromosome 18q gene that is altered in colorectal carcinoma. Science 247: 49–56, 1990.

    Article  PubMed  CAS  Google Scholar 

  71. Cho K. Oliner JD, Simons JW, Hedrick L, Fearon ER, Preisinger AC, Hedge P, Silverman GA and Vogelstein B: The DCC gene-structural-analysis and mutations in colorectal carcinomas. Genomics 19: 525–531, 1994.

    Article  PubMed  CAS  Google Scholar 

  72. Hedrick L. Cho KR, Fearon ER: The DCC gene product in cellular differentiation and colorectal tumorgenesis. Gene Dev 8: 1174–1183, 1994.

    Article  PubMed  CAS  Google Scholar 

  73. Reale MA, Hu G. Zafar AI, Getzenberg RH, Levine SM and Fearon ER: Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues. Cancer Res 54: 4493–4501, 1994.

    PubMed  CAS  Google Scholar 

  74. Pierceall WE, Cho KR, Getzenberg RH, Reale MA, Hedrick L, Vogelstein B and Fearon FR: NIH3T3 cells expressing the deleted in colorectal-cancer tumor-suppressor geneproduct stimulate neurite outgrowth in rat PC 12 pheochromocytoma cells. J Cell Biol 124: 1017–1027, 1994.

    Article  PubMed  CAS  Google Scholar 

  75. Narayanan R, Lawlor KG, Sehaapvel RQ, Cho KR, Vogelstein B, Tran PB-V, Osborne MP and Telang NT: Antisense RNA to the putative tumor-suppressor gene DCC transforms Rat-1 fibroblasts. Oncogene 7: 533–561, 1992.

    Google Scholar 

  76. Miyake K, Inokuchi K, Dan K and Nomura T: Expression of the DCC gene in myelodysplastic syndromes and overt leukemia. Leukemia Res 9: 785–788, 1993.

    Article  Google Scholar 

  77. Miyake S, Nagai K, Yoshino K, Oto M, Endo N and Yuasa Y: Point mutations and allelic deletion of tumor suppressor gene DCC in human esop nageal squamous cell carcinomas and their relation to metastasis. Cancer Res 54: 3007–3010, 1994.

    PubMed  CAS  Google Scholar 

  78. Gima T, Kato H, Honda T, Imamura T, Sasazuki T and Wake N: DCC gene alteration in human endometrial carcinomas. Int J Cancer 57: 480–485, 1994.

    Article  PubMed  CAS  Google Scholar 

  79. Mutty BVVS, Li RG, Houldsworih J, Btronson DL, Reuther VE, Bosl GJ and Chagantik RSK: Frequent allelic deletions and loss of expression characterize the DCC gene in male germ-cell tumors. Oncogene 9: 3227–3231, 1994.

    Google Scholar 

  80. Kim MS, Li S-L, Berlolami CN, Cherrick HM and Park N-H: State of p53, Rb and DCC tumor suppressor genes in human oral cancer cell lines. Anticancer Res 13: 1405–1414, 1993.

    PubMed  CAS  Google Scholar 

  81. Gao X, Honn KV, Grignon D, Sakr W and Chen YQ: Frequent loss of expression and loss of heterozygosity of the putative tumor suppressor gene DCC in prostatic carcinomas. Cancer Res 53: 2723–2727, 1993.

    PubMed  CAS  Google Scholar 

  82. Brewster SF, Browne S and Brown KW: Somatic allelic loss at the DCC, APC, NM23-H1 and P53 tumorsuppressor gene loci in human prostatic-carcinoma. J Urol 151: 1073–1077, 1994.

    PubMed  CAS  Google Scholar 

  83. Kinzler KW, Nilbert MC, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hamilton SR, Hedge P, Markham A, Carlson M, Joslyn G, Groden J, White R, Miki Y, Miyoshi Y, Nishisho I and Nakamura Y: Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. Science 251: 1366–1370, 1991.

    Article  PubMed  CAS  Google Scholar 

  84. Kinzler KW, Nilbert MC, Su L-K, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Flnniear R, Markham A, Groffen J, Boguski MS, Altschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I and Nakamura Y: Identification of FAP locus genes from chromosome 5q21. Science 253: 661–665, 1991.

    Article  PubMed  CAS  Google Scholar 

  85. Groden J, Thliveris A, Samowitz W, Calson M, Gelhert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, Sargeant L, Krapcho K, Wolff E, Burt R, Hughes JP, Warrington J, McPherson J, Wasmuth J, LePaslier D, Abderrahim H, Cohen D, Feppert M and White R: Identfication and characterization of the familial adenomatous polyposis coli gene. Cell 66: 589–600, 1991.

    Article  PubMed  CAS  Google Scholar 

  86. Su LK, Vogelstein B and Kinzler KW: Association of the APC tumor suppressor protein with catenins. Science (Washington DC) 262: 1734–7, 1993.

    Article  CAS  Google Scholar 

  87. Smith KJ, Johnson KA, Bryan TM, Hill DE, Markowitz S, Willson JKV, Paraseeva C, Petersen GM, Hamilion SR, Vogelstein B and Kinzler KW: The APC gene product in normal and tumor cells. Proc Natl Acad Sci USA 90: 2846–2850, 1993.

    Article  PubMed  CAS  Google Scholar 

  88. Joslyn G, Richardson DS, White R, Alber T: Dimer formation by a N-terminal coiled coil in the APC protein. Proc Natl Acad Sci USA 90: 11109–11113, 1993.

    Article  PubMed  CAS  Google Scholar 

  89. Su L-K, Johnson KA, Smith KJ, Hill DE, Vogelstein B and Kinzler KW: Association between wild type and mutant APC gene products. Cancer Res 53: 2728–2731, 1993.

    PubMed  CAS  Google Scholar 

  90. Smith KJ, Levy DB, Maupin P, Pollard TD, Vogelstem B and Kinzler KW: Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res 54: 3672–3675, 1994.

    PubMed  CAS  Google Scholar 

  91. Munemitsu S, Souza B, Miller O, Albert L, Rubinfeld B and Polakis P: The APC gene product associtaes with microtubules in vivo and promotes their assembly in vitro. Cancer Res 54: 3676–3681, 1994.

    PubMed  CAS  Google Scholar 

  92. Groden J, Bhattacharyya NP, Joslyn G, Spirio L, Meuth M and White R: Suppression of tumorigenicity in a human colon-cancer cell-line by introduction of a normal APC gene. J Cellul Biochem (Abs) SI8C: 188, 1994.

    Google Scholar 

  93. Gao X, Zacharek A, Grignon D, Liu H, Sakr W, Porter AT, Chen YQ and Honn KV: High frequency of loss of expression and allelic deletion of the APC and MCC genes in human prostate cancer. Intl J Oncol 6: 111–117, 1995.

    CAS  Google Scholar 

  94. Fong KM, Zimmerman PV and Smith PJ: Tumor progression and loss of heterozygosity at 5q and 18q in non-small cell lung cancer. Cancer Res 55: 220–223, 1995.

    PubMed  CAS  Google Scholar 

  95. Largey JS, Meltzer SJ, Sauk JJ, Hebert CA and Archibald DW: Loss of heterozygosity involving the APC gene in oral squamous-cell carcinomas. Oral Surg Oral Med Oral Pathol 77: 260–263, 1994.

    Article  PubMed  CAS  Google Scholar 

  96. Suzuki H, Aida S, Akimoto S, Igarashi T, Tatani R and Shimazaki J: State of adenomatous polyposis-coli gene and RAS oncogenes in Japanese prostate-cancer. Japanese J Cancer Res 85: 847–852, 1994.

    CAS  Google Scholar 

  97. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, Jones C and Housman DE: Isolation and characterization of a zinc finger polypeptide gene at the human chromosome II Wilms tumor locus. Cell 60, 509–520, 1990.

    Article  PubMed  CAS  Google Scholar 

  98. Eccles MR, Grubb G, Ogawa O, Szeto J and Reeve AE: Cloning of novel Wilms tumor gene (WT1 ) cDNAs; evidence for antisense transcription of WT1. Oncogene 9: 2059–2063, 1994.

    PubMed  CAS  Google Scholar 

  99. Rauscher FJ III, Morris JF, Tournay OE, Cook DM and Curran T: Binding of the Wilms’ tumor locus zinc finger protein to the HGR-1 consensus sequence. Science 250: 1259–62, 1990.

    Article  PubMed  CAS  Google Scholar 

  100. Madden SL, Cook DM, Morris JF, Cashler A, Sukhatme VP and Rauscher FJ: Transcriptional repression mediated by the WT1 Wilms tumor gene product. Science 253: 1550–1553, 1991

    Article  PubMed  CAS  Google Scholar 

  101. Wang Z-Y, Q Q.-Q and Deuel TF: The Wilms tumor gene product WT1 activates or suppresses transcription through separate functional domains. J Biol Chem 268: 9172–9175, 1993.

    PubMed  CAS  Google Scholar 

  102. Werner H, Rauscher FJ 3rd,Sukhatme VP, Drummond IA, Roberts CT Jrand LeRoith D: Transcriptional repression of the insulin-like growth factor I receptor (IGF-I-R) gene by the tumor suppressor WT1 involves binding to sequences both upstream and downstream of the IGL-I-R gene transcription start site. J Biol Chem 269: 12577–12582, 1994.

    PubMed  CAS  Google Scholar 

  103. Dey BR, Sukhatme VP, Roberts AB, Sporn MB, Rauscher FJ 3rd and Kim SJ: Repression of the transforming growth factor-beta 1 gene by the Wilm’s tumor suppressor WTI gene product. Mol Endocrin 8:595–602, 1994.

    Article  CAS  Google Scholar 

  104. Bickmore WA, Oghenc K, Little MH, Seawright A, van Heyningen V and Hastie ND: Modulation of DNA binding specificity by alternative splicing of teh Wilms tumor wtl gene transcript. Science 257:235–237, 1992.

    Article  PubMed  CAS  Google Scholar 

  105. Haber DA and Buckler AJ: WT1: a novel tumor suppressor gene inactivated in Wilms’ tumor. New Biol 4:97–106, 1992.

    PubMed  CAS  Google Scholar 

  106. Gessler M, Konig A, Wualman S, Arden K, Cavenee W and Bruns G: Homozygous inactivation of WTI in a Wilms’ tumor associated with the WAGR syndrome. Gene Chrom Cancer 7:131–136, 1993.

    Article  CAS  Google Scholar 

  107. Shipman R, Schraml P, Colombi M, Raefle G and Ludwig CU: Loss of heterozygosity on chromosome 11 p 13 in primary bladder carcinoma. Hum Genet 91:455–458. 1993.

    Article  PubMed  CAS  Google Scholar 

  108. Fong KM, Zimmerman PV and Smith PJ: Correlation of loss of heterozygosity at 11 p with tumour progression and survival in non-small cell lung cancer. Gene Chrom Cancer 10:183–189, 1994.

    Article  CAS  Google Scholar 

  109. Nordenskjold A, Friedman E and Anvret M: WTI mutations in patients with Denys-Drash syndrome: anovel mutation in exon 8 and parental allele origin. Hum Genetics 93:115–120. 1994.

    CAS  Google Scholar 

  110. Varanasi R, Bardeesy N, Ghahremani M, Petruzzi M-J, Nowak N, Adam MA, Grundy P, Shows TB and Pelletier J: Fine structure analysis of the WTI gene in sporadic Wilms tumors. Proc Natl Acad Sci USA 91:3554–3558, 1994.

    Article  PubMed  CAS  Google Scholar 

  111. Coppes MJ, Campbell CE and Williams BR: The role of WTI in Wilms tumorigenesis. FASEB J, 7:886–895, 1993.

    PubMed  CAS  Google Scholar 

  112. Bruening W, Gros P, Sato T, Stanimir J, Nakamura Y and Housman D: Analysis of the 11 p 13 Wilms’ tumor suppressor gene (WTI) in ovarian tumors. Cancer Invest 11:393–399, 1993.

    Article  PubMed  CAS  Google Scholar 

  113. Park S, Schalling M, Bernard A, Maheswaran S, Shipley GC, Roberts D, Fletcher J, Shipman R, Rheinwald J and Demetri G: The Wilms tumour gene WTI is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma. Nat Genet 4:415–420. 1993.

    Article  PubMed  CAS  Google Scholar 

  114. Wallace MR, Marchuk DA, Anderson LB: Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NFI patients. Science 249, 181, 1990

    Article  PubMed  CAS  Google Scholar 

  115. Xu G, O’Connel P, Viskochil D, Cawthon R, Robertson M, Culver M, Dunn D, Stevens J, Gesteland R, White R and Weiss R: The catalytic domain of the neurofibromatosis type i gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 62:599–608, 1990.

    Article  PubMed  CAS  Google Scholar 

  116. Feig LA and Schaffhausen B: The hunt for Ras targets. Nature 370:508–509, 1994.

    Article  PubMed  CAS  Google Scholar 

  117. Upadhyaya M, Shen M, Cherryson A, Farnham J, Maxnard J, Huson SM and Harper PS: Analysis of mutations at the neurofibromatosis 1 (NFI) locus. Human Molecular Genetics l(9):735–740, 1992.

    Google Scholar 

  118. Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M: A major segment of the neurfibromalosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62:193–201. 1990.

    Article  PubMed  CAS  Google Scholar 

  119. Shannon KM, O’Connell P, Martin GA, Paderanga D, Olson K, Dinndorf P and McCormick F: Loss of the normal NFI allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N Engl J Med 330:597–601, 1994.

    Article  PubMed  CAS  Google Scholar 

  120. Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marinean C, Hoang-Xuan K, Demezuk S, Desmaze C, Plougastel B, Pulst SM, Lenoir G, Bijlsma E, Fashold R, Dumanski J, Jong P, Parry D, Eldrige R, Aurias AA, Delattre O and Thornas G: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363:515–521, 1993.

    Article  PubMed  CAS  Google Scholar 

  121. Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Dley N, Menon AG, Pulaski K, Haase VH, Ambrose CM, Munroe D, Bove C, Haines JL, Martuzas RL, MacDonald ME, Seizinger BR, Short MP, Buckler AJ and Gusella JF: A novel moesin-, ezrin-, radixinlike gene is candidate for the neruofibromatosis 2 tumor supressor. Cell 72:791–800, 1993.

    Article  PubMed  CAS  Google Scholar 

  122. Sainz J, Figuero K, Baser ME, Mautner VF and Pulst S-M: High frequency of nonsense mutations in the NF2 gene caused by to T transitions in five CGA codons. Human Molecular Genetics 4:137–139, 1995.

    Article  PubMed  CAS  Google Scholar 

  123. Latif F, Tory K, Gnarr J, Yao M, Duh F, Orcutt ML, Stack-house T, Kurzmin L, Modi W, Geil L, Schmidt L, Zhou F, Li Hua Wei MH, Chen F, Glenn G, Choyke P, Walther MM, Weng Y, Duan DSR, Dean M, Glavac D, Richards FM, Crossey PA, Ferguson-Smith MA, Paslier DL, Chumakov I, Cohen D, Chinault AC, Maher ER, Lineham WM, Zbar B, and Lerman MI: Identification of the von Hippel-Lindau disease tumor suppressor gene. Science 260:1317–1320, 1993.

    Article  PubMed  CAS  Google Scholar 

  124. Gao J, Naglich JG, Laidlaw J, Whaley JM, Seizinger BR and Kley N: Cloning and characterization of a mouse gene with homology to the human von Hipplel-Lindau disease tumor suppressor gene: implications foir the potential organization of teh human von Hippel-Lindau disease gene. Cancer Res 55:743–747, 1995

    PubMed  CAS  Google Scholar 

  125. Crossey PA, Richards FM, Foster K, Green JS, Prowse A, Lutif F, Leriman ML, Zbar B, Affara NA, Fergusonsmith MA and Maher ER: Identification of intragenic mutations in the Von Hippel-Lindau disease tumor-suppressor gene and correlation with disease phenotype. Hum Mol Genet 3:1303–1308, 1994.

    Article  PubMed  CAS  Google Scholar 

  126. Richard FM, Crossey PA, Phipps ME, Foster K, Latif F, Evans G, Sampson J, Lerman MI, Zbar B, Affara NA and Eerguisonsimith MA: Detailed mapping of germline deletions of the Von Hippel-Lindau disease tumor-suppressor gene. Hum Mol Genet 3:595–598, 1994.

    Article  Google Scholar 

  127. Shuin T, Kondo K, Torigoe S, Kishida T, Kubota Y, Hosaka M, Nagashima Y, Kitamura H, Laiif F, Zbar B, Lerman MI, and Yao M: Frequent somatic mutations and loss of heterozygosity of the Von Hippel-Lindau tumor-suppressor gene in primary human renal-cell carcinomas. Cancer Res 54:2852–2855, 1994.

    PubMed  CAS  Google Scholar 

  128. Gnarra JR, Tory K, Weng Y, Schmidt L, Wei MH, Li H, Latif F, Liu S, Chen F, Duh FM, Lubensky I, Duan DR, Florence C: Mutations of the VHL tumorsuppressor gene in renalcarcinoma. Nat Genet 7:85–90, 1994.

    Article  PubMed  CAS  Google Scholar 

  129. Sekido Y, Bader S, Latif F, Gnarra JR, Gazdar AF, Linehan WM, Zbar B, Lerman ML, Minna LD: Molecular analysis of the Von Hippel-Lindau disease tumor-suppressor gene in human lung-cancer cell-lines. Oncogene 9:1599–1604, 1994.

    PubMed  CAS  Google Scholar 

  130. Tory K, Schmidt L, Chen F, Li H, Hui M, Gnarra J, Latif F, Duh F, Linchan M, Lerman M and Zbar B: Mutation analysis of the von Hippel-Lindau disease (VHL) gene in carcinomas of the kidney lung, breast and ovary. Am J Hum Genet 53:378. 1993.

    Google Scholar 

  131. Zeiger MA, Gnarra JR, Zbar B, Linehan WM and Pass HI: Loss of heterozygosity on the short arm of chromosome-3 in mesothelioma cell-lines and solid tumors. Gene Chrom Cancer 11:15–20. 1994.

    Article  CAS  Google Scholar 

  132. Li XH, Lee NK, Ye YW, Waber PG, Schweitzer C, Cheng QC and Nisen PD: Allelic loss at chromosomes 3p, 8p, 13q, and 17p associated with poor-prognosis at head and neck-cancer. J Nati Cancer Inst 86:1524–1529. 1994.

    Article  CAS  Google Scholar 

  133. Kanno H, Kondo K, Ito S, Yamamoto L, Fujii S, Torigoe S, Sakai N, Hosoka M, Shuin T and Yao M: Somatic mutations of the Von Hippel-Lindau tumor-suppressor gene in sporadic central-nervous-system hemangioblastomas. Cancer Res 54:4845–4847, 1994.

    PubMed  CAS  Google Scholar 

  134. Herman JG, Latif F, Weng Y, Lerman ML, Zbar B, Liu S, Samid D, Dnan DR, Gnarra JR, Linehan M, and Baylin SB: Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sei USA 91:9700–9704, 1994.

    Article  CAS  Google Scholar 

  135. Coleman A, Fountain JW, Noboue T, Olopade OL, Robertson G, Housman DE and Lugo TG: Distinct deletions of chromosome 9p assiociated with melanoma versus glioma. lung cancer, and leukemia. Cancer Res 54:344–348, 1994.

    PubMed  CAS  Google Scholar 

  136. Cannon-Albright LA, Goldgar DE, Neuhausen S, Gruis NA, Anderson DE, Lewis CM, Jost M, Trun TD, Nyguen K and Kamb A: Localization of the 9p melanoma susceptibility locus (MLM) to a 2-cM region between D9S736 and D9S171. Genomics 23:265–268, 1994.

    Article  PubMed  CAS  Google Scholar 

  137. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA: Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368. 753–756. 1994.

    Article  PubMed  CAS  Google Scholar 

  138. Tannin L, Yin J, Zhou X, Suzuki H, Jiang H-Y, Rhyu M-G, Abraham JM, Krasna MJ, Cottrell J and Meltzer SJ:. Frequent loss of heterozygosity on chromosome 9 in adenocarcinoma and squamous cell carcinoma of the esophagus. Cancer Res 54:6094–6096, 1994.

    Google Scholar 

  139. Caldas C, Huhn SA, Dacosta LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruhun RH, Yeo CJ and Kern SE: Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenoeurcinoma. Nature Genetics 8:27–32. 1994. [Correction appears in 8: 410. 1994.]

    Article  PubMed  CAS  Google Scholar 

  140. Huang DP, Lo K-WL, Hasselt A van, Woo JKS, Choi PHK, Leung S-F, Cheung S-T, Cairns P, Sidransky D and Lee JCK: A region of homozygous deletion ofn chromosome 9p21-22 in primary nasopharyngeal carcinoma. Cancer Res 54;4003–4006, 1994.

    PubMed  CAS  Google Scholar 

  141. Merlo A, Gabrielson E, Askin F and Sidransky D: Frequent loss of chromosome 9 in human primary non-small cell lung cancer. Cancer Res 54:640–642. 1994.

    PubMed  CAS  Google Scholar 

  142. Shapiro GI, Edwards CD, Kobzik L, Godleski J, Richards W, Sugarbaker KJ and Rollins BJ: Reciprocal Rb inactivation and pl6INK4 expression in primary lung cancers and cell lines. Cancer Res 55:505–509, 1995.

    PubMed  CAS  Google Scholar 

  143. Washimi O, Nagatake M, Osada H, Ueda R, Koshikawa T, Seki T, Takahashi T and Takahushi T: In vivo occurrence of pl6 (MTS1) and pl5 (MTS2) alterations preferentially in non-small cell lung cancers. Cancer Res 55:514–517, 1995.

    PubMed  CAS  Google Scholar 

  144. Knowles MA, Elder PA, Williamson M, Cairns JP, Shaw ME and Law MG: Allelotype of human bladder cancer. Cancer Res 54:531–538. 1994.

    PubMed  CAS  Google Scholar 

  145. Cairns P, Mao L, Merlo A, Lee DJ, Schwab D, Eby Y, Tokino K, van der Riet P, Blaugrund JE and Didransky D: Rates of pl6(MTSl) mutations in primary tumors with 9p loss. Science 415–416. 1994.

  146. Spruck CH III, Ohneseit PF, Gonzalez M, Esrig D, Miyai N, Tsui YC, Lerner SP, Schnuitte C, Yang AS, Cote R, Debeau L, Nichols PW, Hermann GG, Steven K, Horn T, Skinner DG and Jones PA: Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res 54:784–788. 1994.

    PubMed  CAS  Google Scholar 

  147. Devlin J, Keen AJ and Knowles MA: Homozygous deletion mapping at 9p21 in bladder carcinoma defines a critical region within 2 cM of IFNA. Oncogene 9:2757–2760. 1994.

    PubMed  CAS  Google Scholar 

  148. Cairns P, Tokino K, Eby Y and Sidransky D: Localization of tumor suppressor loci on chromosome 9 in promary human renal celll carcinomas. Cancer Res 55:224–227. 1995.

    PubMed  CAS  Google Scholar 

  149. Jen J, Harper W, Bigner SH, Bigner DD, Papadopoulos N, Markowitz S, Willson JKV, Kinzler KW and Vogelstein B: Deletion of p16 and p15 genes in brain tumors. Cancer Res 54:6353–6358, 1994.

    PubMed  CAS  Google Scholar 

  150. Schmidt EE, Ichiniuni K, Reifenberger G, and Collins VP: CDKN2 (pl6/MTSl) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res 54:6321–6324, 1994.

    PubMed  CAS  Google Scholar 

  151. Walker DG, Duan W, Popovic EA, Daye AH, Tomlinson FH, and Lavin M:Homozygous deletions of the multiple tumor suppressor gene 1 in the progression of human astroeytomas. Cancer Res 55:22–23, 1995.

    Google Scholar 

  152. Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee WC, Altomare DA, Nobori T, Olopade OI, Buckler AJ, and Testa JR. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res 54:5547–5551, 1994.

    PubMed  CAS  Google Scholar 

  153. Weaver-Feldhaus J, Gruis NA, Neuhausen S, Pasliar DL, Stockart E, Skolnick MH, and Kamb A: Localization of a putative tumor suppressor by using homozygous deletion in melanomas. Proc Natl Acad Sci USA 91:7563–7567, 1994.

    Article  PubMed  CAS  Google Scholar 

  154. Kamb A, Gruis N, Weaver-Feldhaus J, Lin Q, Hurshman K, Tavitigian SV, Stockert E, Day RS, Johnson BE, Skolnick MH: A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440, 1994.

    Article  PubMed  CAS  Google Scholar 

  155. Serrano M, Hamon GJ, and Beach D: A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707, 1993.

    Article  PubMed  CAS  Google Scholar 

  156. Kamb A, Shattuckeidens D, EEles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaverfeldhaus J, Mcclure M, Aitken JF, Anderson DE, Bergman W, Frants R, Goldgar DE, Green A, Maclennan R, Martin NG, Meyer LJ, Youl P, Zone JJ, Skolnick MH, and Cannonalbright LA: Analysis of the pl6 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8:22–26, 1994.

    Article  CAS  Google Scholar 

  157. Hussussian CJ, Struewing JP, Goldstein AM, Higgins PAT, Ally DS, Sheahan MD, Clark WH, Tucker MA, and Dracopoli NC: Germline pl6 mutations in familial melanoma. Nat Genet 8:15–21, 1994.

    Article  PubMed  CAS  Google Scholar 

  158. Giani C and Finocchiaro G: Mutation rate of the CDKN2 gene in malignant gliomas. Cancer Res 54:6338–6339, 1994.

    PubMed  CAS  Google Scholar 

  159. Mori T, Miura K, Aoki T, Nishihira T, Mori S, and Nakamura Y: Frequent somatic mutation of the MTSI/CDK4I (multiple tumor suppressor/cyclin-dependent dinase 4 inhibitor) gene in esophageal squamous cell carcinoma. Cancer Res 54:3396–3397, 1994.

    PubMed  CAS  Google Scholar 

  160. Zhou X, Tannin L, Yin J, Jiang H-Y, Suzuki H, Khyu M-G, Abraham JM, Meltzer SJ: The MST1 gene is frequently mutated in primary human esophageal tumors. Oncogene 9:3737–3741, 1994.

    PubMed  CAS  Google Scholar 

  161. Sprunck CHIII, Gonzalez-Zudueta M, Shibata A, Simoneau AR, Lin M-F, Gonzales F, Tsai YC and Jones PA: p16 gen in uncultured tumours. Nature 370. 183–184, 1994.

    Article  Google Scholar 

  162. Otterson GA, Kratzke RA, Coxon A, Kim YW, and Kaye FJ: Absence of pl6(lNK4) protein is restricted to the subset of lung-cancer lines that retains wildtype RB. Oncogene 9:3375–3378, 1994.

    PubMed  CAS  Google Scholar 

  163. Hannon GJ, and Beach D: pl5INK4B is a potential effector of TGF-b-induced cell cycle arrest. Nature 371: 257–261, 1994.

    Article  PubMed  CAS  Google Scholar 

  164. Otsuki T, Clark HM, Wellmann A, Jaffe ES, and Ruffeld M: Involvement of CDKN2 ( p 16INK4A /MTS 1) and pl5INK4B/MTS2 in human leukemias and lymphomas. Cancer Res 55: 1436–1440, 1995.

    PubMed  CAS  Google Scholar 

  165. Okamoto A, Hussain SP, Hagiwara K, Spillare EA, Rusin MR, Demetrick DI, Serrano M, Hannon GJ, Shiseki M, Zari-wala M, Xiong Y, Beach DH, Yokota J and Harris CC: Mutations in the pl6INR4/MTSI/CDKN2. pl5INR4B/MTS2, and p18 genes in primary and metastatic lung cancer. Cancer Res 55: 1414–1451, 1995.

    Google Scholar 

  166. Zhang W, Graso L, McClain CD, Gambel AM, Cha Y, Travail S, Deisseroth AB and Mercer WE: p53-independent inducton of WAF/CIP1 in human leukemia cells is correlated with groth arrest accompaning monocyte/macrophage differentiation. Cancer Res 55: 668–674, 1995.

    PubMed  CAS  Google Scholar 

  167. Parker SB, Eichele G, Zhang P, Rawls A, Sands AT, Bradley A, Olson EN, Harper JW and Elldge SJ: p53-independent expression of p21Cip in muscle and other terminally differentiation cells. Science 267: 1024–1027, 1995.

    Article  PubMed  CAS  Google Scholar 

  168. Halevy O, Novilch BG, Spicer DB, Skapek SX, Rhee J, Hannon GJ, Beach D, and Eassar AB: Correleation of terminal cell cycle arrest of skeletal muscle with induction of p21 by MyoD. Science 267: 1018–1021, 1995.

    Article  PubMed  CAS  Google Scholar 

  169. Polyak K, Kato J, Solomon MJ, Sherr CJ, Massague J, Roberts JM and Koff A: p27Nip1, a cyclin-Cdk inhibitor, links transorming growth factor-b and Contact inhibition to cell cycle arrest. Gene Devel 8: 9–22, 1993.

    Article  Google Scholar 

  170. Polvak K, Eee M-H, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, and Massague J: Cloning op27Kipt, a cyclindependent kinase inhibitor and a protential mediator of exrtacellular antimitogenic signals. Cell 78: 59–66, 1994.

    Article  Google Scholar 

  171. Toyoshima H and Hunter T: p27, a novel inhibitor of Gl cyclin-Cdk protein kinase activity, is related to p21. Cell 78: 67–74, 1994.

    Article  PubMed  CAS  Google Scholar 

  172. Nourse J, Eirpo E, Flanagan WM, Coats S, Polyak K, Lee M-H, Massague J, Crabtree GR and Roberts JM: Interleukin-2-mediated elimination of the p27Kipt eyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372: 570–573, 1994.

    Article  PubMed  CAS  Google Scholar 

  173. Hengst L, Dudic V, Slingerland JM, Lees E, and Reed SI: A cell cycle-regulated inhibitor of eyclin-dependent kinases. Proc Natl Acad Sci USA 91: 5291–5295, 1994.

    Article  PubMed  CAS  Google Scholar 

  174. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B and King, M-C: Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250: 1684–1689, 1990.

    Article  PubMed  CAS  Google Scholar 

  175. Tonin P, Seroya O, Simard J, Lenoir G, Fetontun J, Morgan K, Lynch H and Narod S: The gene for hereditary breastovarian cancer. BRCA1. maps distal to EDH17B2 in chromosome region 17ql2-q2l. Hum Mol Genet 3: 1679–1682, 1994.

    Article  PubMed  CAS  Google Scholar 

  176. Neuhmsen SL, and Marshall CJ: Loss of heterozygosity in familial tumors from three BRCA1-linked kindreds. Cancer Res 54: 6069–6072, 1994.

    Google Scholar 

  177. Neuhanusen SL, Swensen J, Miki Y, Liu Q, Tavtigian S, Shatluck-Eidens D, Kamb A, Hobbs MR, Gingrich J, Shizuya H, Kim UJ, Cochran C, Futreal PA, Wiseman RW, Lynch HT.Tonin P, Narod S, Cannon-Albright L, Skolnick MH and Goldgar DE: A PI-based physical map of the region from D17S776 to D17S78 containing the breast cancer susceptibility gene BRCA1. Hum Mol Genet 3: 1919–1926, 1994.

    Article  Google Scholar 

  178. Simard J, Tonin P, Durocher E, Morgan K, Rommens J, Gingras S, Samson C, Leblanc J-E, Belanger C, Kion F, Liu Q, Skolnick M, Goldgar D, Shattuck-Eidens D, Labrie F and Narod SA: Common origins of BRCAI mutations in Canadian breast and ovarian cancer families. Nat Genet 8: 393–398, 1994.

    Article  Google Scholar 

  179. Goldgar DE, Fields P, Lewis CM, Tran TD, Cannonalhright LA, Ward JH, Swensen J and Skolnick MH: A large kindred with I7q-linked breast and ovarian-cancer-genetic, phenotypic. and geneological analysis. J Natl Cancer Inst 86: 200–209, 1994.

    Article  PubMed  CAS  Google Scholar 

  180. Arason A, Barkardottir RB and Egilsson V: Lindage analysis of chromosome I7q marders and breast-ovarian cancer in icelandic families, and possible relationship to prostaticcancer. Am J Hum Genet 52: 711–717, 1993.

    PubMed  CAS  Google Scholar 

  181. Friedaman LS, Ostermeyer EA, Lynch ED, Szabo Cl, Anderson LA, Dowd P, Lee MK, Rowell SE, Boy J., and King M-C: The search for BRCAI. Cancer Res 54: 6374–6382, 1994.

    Google Scholar 

  182. Gao X, Zacharek A, Salkowski A, Grignon D, Sakr W, Porter AT and Honn KV: Loss of heterozygosity of the BRCAI and other loci on chromosome 17q in human prostate cancer. Cancer Res 55: 1002–1005, 1995.

    PubMed  CAS  Google Scholar 

  183. Vogelstein B and Kinzler KW: Has the breast cancer gene been found. Cell 79: 1–3, 1994.

    Article  PubMed  CAS  Google Scholar 

  184. Zeladahedman M, Torroella M, Mesquita R, Nordenshjold M, Skoog L, and Lindblom A: Loss of heterozygosity studies in tumors from famileis with breast-ovarian cancer syndrome. Hum Genet 94: 231–234, 1994.

    CAS  Google Scholar 

  185. Friedman LS, Ostermeyer EA, Szabo CL, Dowd P, Lynch ED, Rowell SE and King M-C: Confirmation of BRCAI by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet 8: 399–404, 1994.

    Article  PubMed  CAS  Google Scholar 

  186. Davies K: Damage report for BRCAI. Nature 372: 574, 1994.

    Article  CAS  Google Scholar 

  187. Castillo LH, Couch FJ, Erdos MR, Hoskins KF, Calzone K, Garber JE, Boyd J, Lubin MB, Deshano ML, Brady LC, Collins FS and Weber BE: Mutations in the BRCAI gene in families with early-onset breast and ovarian cancer. Nat Genet 8: 387–391, 1994.

    Article  Google Scholar 

  188. Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Taytigian K, Bennett S, Hauge-Strano A, Swensen J, Miki Y, Eddington K, MeClure M, Frye C, Weaver-Feldhaas J, Ding W, Gholami Z, Soderkvist PJ, Terry L, Jhanwar S, Berchuck A, Ihlehard JD, Marks J, Ballinger DG, Barrett JC, Skolnick MH, Kamh A and Wiseman R: BRCAI mutations in primary breast and ovarian carcinomas. Science 266: 120–122, 1994.

    Article  PubMed  CAS  Google Scholar 

  189. Cropp CS, Nevanlinna HA, Pyrhonen S, Stenman U-H, Salmikangas P, Albertsen H, White R and Caliban R: Lvidence for involvement of BRCAI in sproadic breast carcinomas. Cancer Res 54: 2548–2551, 1994.

    PubMed  CAS  Google Scholar 

  190. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D.Field P, Marshall G, Narod S, Lenoir GM, Lynch H, Feunteun J, Deville P, Cornelisse CJ, Nenko FH, Daly PA, Ormiston W, McManus R, Pye C, Lewis CM, Cannonalhright LA, Peto J, Ponder BAJ, Skolnick MH, Easton DF, Goldgar DE, and Stratton MR: Localization of a breast-cancer susceptibility gene. BRCA2, to chromosome 12ql2-13. Science 265: 2088–2090, 1994.

    Article  PubMed  CAS  Google Scholar 

  191. Swift M, Marrell D, Massey RB, Chase CL: Incidence of cancer in 161 families affected by atazxia-telangiectasia. N Eng J Med 325. 1831–1836, 1991.

    CAS  Google Scholar 

  192. Strattan MR, Ford D, Neuhasen S, Seal S, Wooster R, Friedman LS, King MC, Egilsson V, Devillee P, McManus R, Daly PA, Smyth E, Ponder BAJ, Peto J, Cannonalbright L, Easton DE, and Goldgar DE: Familial male breast-cancer is not linked to the BRCAI locus on chromosome 17q. Nat Genet 7: 103–107, 1994.

    Article  Google Scholar 

  193. Ford D, Easton DE, Bishop DT, Narod SA, Goldgar DE, Haites N, Milner G, Allan L, Ponder BAJ, Peto J, Smith S, Stratton M, Linoir GM, Eeunteun J, Lynch H, Arason A.Bar-kardottir R, Ggilsson V.Black DM, Kelsell D, Spurr N.Devilee P, Cornelisse CJ, Varsen H, Birch JM, Skolnick M, Santiba-nezkoref MS, Teare D, Steel M, Porter D, Cohen BB, Carothers A, Smyth E, Weber B, Newbold B, Boehuke M, Collins ES, Cannonalbright LA, and Goldgar D: Risks of cancer in BRCAI-mutation carriers. Lancet 343: 692–695, 1994.

    Article  PubMed  CAS  Google Scholar 

  194. Sanchez Y, El-Naggar A, Pathak S and Killary AM: A tumor suppresser locus within 3pl4-pl2 mediates rapid cell dath of renal cell carcinoma in vivo. Proc Natl Acad Sci USA 91: 3383–3387, 1994.

    Article  PubMed  CAS  Google Scholar 

  195. Maestro R, Gasparotto D, Vukosavljevic T, Barzan L, Suljaro S, and Boiocchi M: Three discrete regions of deletion at 3p in head and neck cancers. Cancer Res 53: 5775–5779, 1993.

    PubMed  CAS  Google Scholar 

  196. Yoo, GH, Xu H-J, Brennan JA, Westra W, Hruban RH, Koch W, Benedict WF and Sidransky D: Infrequent inactivation of the retinoblastoma gene despite frequent loss of chromosome 13q in head and neck squamous cell carcimoma. Cancer Res 54: 4603–4606, 1994.

    PubMed  CAS  Google Scholar 

  197. Akopian K and Kouyoumdjian JC: Human non-small-cell lung cancer are frequently associated with loss of heterozygosity in the 5q(34-terminal) chromosomal region. Cancer Mole Biol 1: 173–177, 1994.

    Google Scholar 

  198. Shanley SM, Dawkins H, Wainwright BJ, Wicking C, Heenum P, Eldon M, Searte J, and Chenevix-Trench G: Fine deletion mapping of the long arm of chromosome 9 in sporadic and familial basal cell carcinoas. Hum Mol Genet 4: 129–133, 1995.

    Article  PubMed  CAS  Google Scholar 

  199. Hampton GM, Penny LA, Baergen RN, Larson A, Brewer C, Liao S, Busby-Earle, RMC Williams, AWR, Steel CM, Bird CC.Stasnbridge EJ and Evans G: A. Loss of heterozygosity in cervical carcinoma: subchromosomal localizain of a putative tumor-suppressor gene to chromosome 11q22-q24. Proc Natl Acad Sci USA 91: 6953–6957, 1994.

    Article  PubMed  CAS  Google Scholar 

  200. Bieche I, Champeine M-H and Lidereau R: A tumor suppressor gene on chromosome 1p32-pter controls tha amplification of MYC family gene in breast cancer. Cancer Res 54: 4274–44276, 1994.

    PubMed  CAS  Google Scholar 

  201. Zhuang Z, Merino MJ, Chuaqui R, Liotta LA and Ennnerl-Bitck MR: Identical allelic loss on chromosome 11q13 in microdisseeted in situ and invasive human brteast cancer. Cancer Res 55: 467–471, 1995.

    PubMed  CAS  Google Scholar 

  202. Hampton, G M.Mannennaa A, Winquuist R, Alavaikko M, Blanco G, Taskinen PJ, Kiviniemi H, Newsham I.Cavenee WK and Evans GA: Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Res 54: 4586–4589, 1994.

    PubMed  CAS  Google Scholar 

  203. Tsuda H, Callen DF, Fukutomi I, Makamura Y and Hirohasiu S: Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers irrespectively of differences in phenotype and extent of spread. Cancer Res 54: 513–517, 1994.

    PubMed  CAS  Google Scholar 

  204. von Deimling A.Louis DN, von Amman K, Petersen I, Wiestler DO, Seizinger BR: Evidence for a tumor suppressor gene on chromosome 19q associated with human asrrocytomas, oligodendrogliomas. and mixed gliomas. Cancer Res 52: 4277–4279, 1992.

    Google Scholar 

  205. Kunimi K, Bergerheim USR, Larsson I-L, Ekman P, and Collins VP: Allotyping of human prostatic adenocarcinoma. Genomics 11: 530–536, 1991.

    Article  PubMed  CAS  Google Scholar 

  206. Bergerheim USR, Kumimi K, Collins VP and Ekman P: Deletion mapping of chromosomes 8. 10. and 16 in human prostatic carcinoma. Gene Chrom Cancer 3: 215–220, 1993.

    Article  Google Scholar 

  207. Gao X, Wu N, Grignon D, Sakr W, Porter AT and Honn KV: Allelic deletion of microsatellite loci on chromosome 6p in a subset of human prostate cancer. Cancer Mol Biol. 1: 297–304, 1994.

    CAS  Google Scholar 

  208. El-Deiry WS, Harper W, O’Connor PM, Velculescn VE, Canman CE, Jachnan J, Pietenopol JA, Bnrrell M, Hill BE, Wang Y, Wiman KG, Mercer WE, Kastan MB, Kohn KW, Elledge SJ, Kinzler KW and Vogelstein B: WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54: 1169–1174, 1994.

    PubMed  CAS  Google Scholar 

  209. Trapmam J, Sleddens HFBM, van der Weiden MM, Dinjens WMN, Konig JJ, Schroder FH, Faber PW, and Bosnian FT: Loss of heterozygosity of chromosome 8 microsatellite loci implicates a candidate tumor suppressor gene between the loci D8S87 and D8S133 in human prostate cancer. Cancer Res 54: 6061–6064, 1994.

    Google Scholar 

  210. Bova GS, Carter BS.Bussemakers MJG, Emi M, Enjiwara Y, Kyprianou N, Jacobs SC, Robinson JC, Epstein JI, Walsh PC and Isaacs WB: Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer. Cancer Res 53: 3869–73, 1993.

    PubMed  CAS  Google Scholar 

  211. Macgrogan D, Levy A, Bostwick D, Wagner M, Wells D, and Bookstein R: Loss of chromosome arm 8p loci in prostatecancer-mapping by quantitative allelic imbalance. Gene Chrom Cancer 10: 151–159, 1994.

    Article  CAS  Google Scholar 

  212. Matsuyama H, Pan Y, Skoog L, Tribukait B, Naito K, Ekman P, Lichter P, and Bergerheim USR: Deletion mapping of chromosome 8p in prostate-cancer by fluorescence in-situ hybridization. Oncogene 9: 3071–3076, 1994.

    PubMed  CAS  Google Scholar 

  213. Bova GS, Bussmakers MJG, Robinson JC, MacGrogan D, Levy A, Bookstein R, Isaacs WB: Homozygous deletion mapping of a one megabase region of 8p22 in a human prostate cancer. Abst. Book. Basic and clinical aspects of prostate cancer. Palm Springs CA USA Abstract No. A-4. December 8–12. 1994.

  214. Zenklusen JC, Thompson JC, Troncoso P, Kagan J, and Conti, CJ: Loss of Heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1. Cancer Res 54: 6370–6373, 1994.

    PubMed  CAS  Google Scholar 

  215. Rinker-Schaeffer CW, Hawkins AL, Ru N, Dong J, Stoica G, Griffin CA, Ichikawa T, Barrett JC and Isaacs JT: Differential suppression of mammary and prostate cancer metastasis by human chromosomes 17 and II Cancer Res 54: 6249–6256, 1994.

    PubMed  CAS  Google Scholar 

  216. Dong J-T, Lamb PW, Rinker-Schaeffer CW.Vukanovic J, Isaacs JT.Barrett JC: KAII a metastasis suppressor gene for prostate cancer on human chromosome 11pl1.2. Science 268: 799–800, 1995.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Wayne State University, School of Medicine, 48202, Detroit, MI

    Xiang Gao & Kenneth V. Honn

  2. Gershenson Radiation Oncology Center, Harper Hospital, Detroit Medical Center, 48201, Detroit, MI

    Kenneth V. Honn

  3. Department of Pathology, Wayne State University, School of Medicine, 48202, Detroit, MI

    Kenneth V. Honn

  4. Department of Chemistry, Wayne State University, School of Medicine, 48202, Detroit, MI

    Kenneth V. Honn

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  1. Xiang Gao
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  2. Kenneth V. Honn
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Gao, X., Honn, K.V. Recessive oncogenes: Current status. Pathol. Oncol. Res. 1, 7–22 (1995). https://doi.org/10.1007/BF02893578

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  • DOI: https://doi.org/10.1007/BF02893578

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