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Genetic and Cytogenetic Analyses of Breast Cancer Yield Different Perspectives of a Complex Disease

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Abstract

Genomic instability in breast cancer results in low-level changes in DNA copy number, a significant but poorly understood mechanism underlying the genetic heterogeneity of this disorder. Two different approaches, loss of heterozygosity (LOH) and comparative genomic hybridization (CGH), have been used to probe the genetics of breast cancer evolution. LOH is a locus specific method that detects the variation in the parental origin of DNA, but is not quantitative. CGH provides a genome-wide accounting of the magnitude of DNA copy number changes, but not parental origin. Both methods have identified complex and heterogeneous patterns of DNA losses, duplications, and amplifications during breast cancer evolution. LOH and CGH technologies interrogate very distinct mechanisms driving breast tumor evolution, yet are seldom used in parallel to profile specimens. Thus, the relative significance of genetic versus numerical variations of DNA in breast cancer evolution remains undefined. This review will attempt to summarize some of the successes of these investigations, highlight some complex and confounding observations emerging from these studies, and discuss the potential of these studies to improve our understanding of breast cancer biology and treatment.

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References

  1. American Cancer Society: ACS Cancer facts and figures. Cancer Pract 8: 105-107, 2000

    Google Scholar 

  2. Geryk J, Dezelee P, Barnier JV, Svoboda J, Nehyba J, Karakoz I, Rynditch AV, Yatsula BA, Calothy G: Transduction of the cellular src gene and 3′ adjacent sequences in avian sarcoma virus PR2257. J Virol 63: 481-492, 1989

    Google Scholar 

  3. Parker RC, Varmus HE, Bishop JM. Cellular homologue (csrc) of the transforming gene of Rous sarcoma virus: isolation, mapping, and transcriptional analysis of c-src and flanking regions. Proc Natl Acad Sci USA 78: 5842-5846, 1981

    Google Scholar 

  4. Peehl DM, Stanbridge EJ. Characterization of human keratinocyte ×HeLa somatic cell hybrids. Int J Cancer 27: 625-635, 1981

    Google Scholar 

  5. Marshall CJ, Sager R: Genetic analysis of tumorigenesis: IX suppression of anchorage independence in hybrids between transformed hamster cell lines. Somatic Cell Genet 7: 713-723, 1981

    Google Scholar 

  6. Zajchowski DA, Band V, Trask DK, Kling D, Connolly JL, Sager R: Suppression of tumor-forming ability and related traits in MCF-7 human breast cancer cells by fusion with immortal mammary epithelial cells. Proc Natl Acad Sci USA 87: 2314-2318, 1990

    Google Scholar 

  7. Bader SA, Fasching C, Brodeur GM, Stanbridge EJ: Dissociation of suppression of tumorigenicity and differentiation in vitro effected by transfer of single human chromosomes into human neuroblastoma cells. Cell Growth Differ 2: 245-255, 1991

    Google Scholar 

  8. Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL: Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305: 779-784, 1983

    Google Scholar 

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

    Google Scholar 

  10. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323: 643-646, 1986

    Google Scholar 

  11. Lee W-H, Bookstein R, Hong F, Young LJ, Shew JY, Lee EY: Human retinoblastoma susceptibility gene: cloning, identifi-cation, and sequence. Science 235: 1394-1399, 1987

    Google Scholar 

  12. Lee W-H, Shew J-Y, Hong FD, Sery TW, Donoso LA, Young LJ, Bookstein R, Lee EY: The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature 329: 642-645, 1987

    Google Scholar 

  13. Saiki R, Scharf S, Taloona F, Mullis K, Horn G, Erlich H, Arnheim N: Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 230: 1150-1154, 1985

    Google Scholar 

  14. Weber J, May PE: Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44: 388-396, 1989

    Google Scholar 

  15. Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M: A second-generation linkage map of the human genome. Nature 359: 794-801, 1992

    Google Scholar 

  16. Hudson T, Stein L, Gerety S, Ma J, Castle A, Silva J, Slonin DK, Baptista R, Kruglyak L, Xu SH: An STS-based Map of the Human Genome. Science 270: 1945-1954, 1995

    Google Scholar 

  17. Wright DK, Manos MM: Sample preparation from paraffin embedded tissues. In: Innes MA, Gelfand DH, Sninsky JJ, White TJ (eds) PCR Protocols. Academic Press, San Diego, 1990, pp 53-158

    Google Scholar 

  18. Emmert-Buck MR, Bonner RF, Smith PD, Chuaqui RF, Zhuang Z, Goldstein SR, Weiss RA, Liotta LA: Laser Capture Microdissection. Science 274: 998-1001, 1996

    Google Scholar 

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

    Google Scholar 

  20. Fountain JW, Karayiorgou M, Ernstoff MS, Kirkwood JM, Vlock DR, Titus-Ernstoff L, Bouchard B, Vijayasaradhi S, Houghton AN, Lahti J, Kidd VJ, Housman DE, Dracopoli NC: Homozygous deletions within human chromosome band 9p21 in melanoma. Proc Natl Acad Sci USA 89: 10557-10561, 1992

    Google Scholar 

  21. Bell DW, Varley JM, Szydlo TE, Kang DH, Wahrer DCR, Shannon KE, Lubratovich M, Verselis SJ, Isselbacher KJ, Fraumeni JF, Birch JM, Li FP, Garber JE, Haber DA: Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science 286: 2528-2531, 1999

    Google Scholar 

  22. Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, Robertson M, Dunn D, Gesteland R, O‘Connell P, White R: A major segment of the neurofibromatosis type 1 gene: cDNA sequence genomic structure and point mutations. Cell 62: 193-201, 1990

    Google Scholar 

  23. Viskochil D, Buchberg AM, Xu G, Cawthon RM, Stevens J, Wolff RK, Culver M, Carey JC, Copeland NG, Jenkins NA, White R, O‘Connell P: Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62: 187-192, 1990

    Google Scholar 

  24. Wallace MR, Marchuk DA, Andersen LB, Letcher R, Odeh HM, Saulino AM, Fountain JW, Brereton A, Nicholson J, Mitchell AL, Gutmann DH, Boguski M, Collins FS: Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249: 181-186, 1990

    Google Scholar 

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

    Google Scholar 

  26. Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert 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, Le Paslier D, Abderrahim H, Cohen D, Leppert M, White R: Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66: 589-600, 1991

    Google Scholar 

  27. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal 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, Ward 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, Skolnick MH: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 66-71, 1994

    Google Scholar 

  28. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G, Barfoot R, Hamoudi R, Patel S, Rice C, Biggs P, Hashim Y, Smith A, Connor F, Arason A, Gudmundsson J, Ficenec D, Keisell D, Ford D, Tonin P, Bishop DT, Spurr NK, Ponder BAJ, Eeles R, Peto J, Devilee P, Cornelisse C, Lynch H, Narod S, Lenoir G, Egilsson V, Barkadottir RB, Easton DF, Bentley DR, Futreal PA, Ashworth A, Stratton MR: Identification of the breast cancer susceptibility gene BRCA2. Nature 378: 789-792, 1995

    Google Scholar 

  29. Kallioniemi OP, Kallioniemi A, Sudar D, Rutovitz D, Gray JW, Waldman F, Pinkel D: Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. Semin Cancer Biol 4: 41-46, 1993

    Google Scholar 

  30. Tirkkonen M, Tanner M, Karhu R, Kallioniemi A, Isola J, Kallioniemi OP: Molecular cytogenetics of primary breast cancer by CGH. Genes Chrom Cancer 21: 177-184, 1998

    Google Scholar 

  31. Larramendy ML, Lushnikova T, Björkqvist A-M, Wistuba II, Virmani AK, Shivapurkar N, Adi F, Gazdar AF, Knuutila S: Comparative genomic hybridization reveals complex genetic changes in primary breast cancer tumors and their cell lines. Cancer Genet Cytogenet 119: 132-138, 2000

    Google Scholar 

  32. Richard F, Pacyna-Gengelbach M, Schluns K, Fleige B, Winzer KJ, Szymas J, Dietel M, Petersen I, Schwendel A: Patterns of chromosomal imbalances in invasive breast cancer. Int J Cancer 89: 305-310, 1989

    Google Scholar 

  33. Aubele M, Mattis A, Zitzelsberger H, Walch A, Kremer M, Welzl G, Hofler H, Werner M: Extensive ductal carcinoma in situ with small foci of invasive ductal carcinoma: evidence of genetic resemblance by CGH. Int J Cancer 85: 82-86, 2000

    Google Scholar 

  34. Pinkel D, Segraves R, Sudar D, Clark S, Poole I, Kowbel D, Collins C, Kuo WL, Chen C, Zhai Y, Dairkee SH, Ljung BM, Gray JW, Albertson DG: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat Genet 20: 207-211, 1998

    Google Scholar 

  35. Cai WW, Mao J-H, Chow C-W, Damani S, Balmain A, Bradley A: Genome wide detection of chromosomal imbalances in tumors using BAC microarrays. Nature Biotech 19: 392-396, 2002

    Google Scholar 

  36. Fan JB, Chen X, Halushka MK, Berno A, Huang X, Ryder T, Lipshutz RJ, Lockhart DJ, Chakravarti A: Parallel genotyping of human SNPs using generic high-density oligonucleotide tag arrays. Genome Res 10: 853-860, 2000

    Google Scholar 

  37. Sapolsky RJ, Hsie L, Berno A, Ghandour G, Mittmann M, Fan JB: High-throughput polymorphism screening and genotyping with high-density oligonucleotide arrays. Genet Anal 14: 187-192, 1999

    Google Scholar 

  38. Dong S, Wang E, Hsie L, Cao Y, Chen X, Gingeras TR: Flexible use of high-density oligonucleotide arrays for singlenucleotide polymorphism discovery and validation. Genome Res 11: 1418-1424, 2001

    Google Scholar 

  39. Deng G, Lu Y, Zlotnikov G, Thor AD, Smith HS: Loss of heterozygosity in normal tissue adjacent to breast carcinomas. Science 274: 2057-2059, 1996

    Google Scholar 

  40. Fuqua SAW, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O‘Connell P, Allred DC: A hypersensitive estrogen receptor mutation in premalignant breast lesions. Cancer Res 60: 4026-4029, 2000

    Google Scholar 

  41. Kurose K, Hoshaw-Woodard S, Adeyinka A, Lemeshow S, Watson PH, Eng C, Genetic model of multi-step breast carcinogenesis involving the epithelium and stroma: clues to tumour-microenvironment interactions. Hum Mol Genet 10: 1907-1913, 2001

    Google Scholar 

  42. Lee J-H, Welch DR: Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1. Cancer Res 57: 2384-2387, 1997

    Google Scholar 

  43. Jensen DE, Proctor M, Marquis ST, Gardner HP, Ha SI, Chodosh LA, Ishov AM, Tommerup N, Vissing H, Sekido Y, Minna J, Borodovsky A, Schultz DC, Wilkinson KD, Maul GG, Barlev N, Berger SL, Prendergast GC, Rauscher III FJ: BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. Oncogene 16: 1097-1112, 1998

    Google Scholar 

  44. Varrault A, Ciani E, Apiou F, Bilanges B, Hoffmann A, Pantaloni C, Bockaert J, Spengler D, Journot L: hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancer. Proc Natl Acad Sci USA 95: 8835-8840, 1998

    Google Scholar 

  45. Still IH, Hamilton M, Vince P, Wolfman A, Cowell JK: Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene 18: 4032-4038, 1999

    Google Scholar 

  46. Forozan F, Veldman R, Ammerman CA, Parsa NZ, Kallioniemi A, Kallioniemi OP, Ethier SP: Molecular cytogenetic analysis of 11 new breast cancer cell lines. Br J Cancer 81: 1328-1334, 1999

    Google Scholar 

  47. Yokota J, Tsunetsugu-Yokota Y, Battifora H, Le Fevre C, Cline MJ: Alterations of myc, myb, and ras(Ha) proto-oncogenes in cancers are frequent and show clinical correlation. Science 231: 261-265, 1986

    Google Scholar 

  48. Cairns P, Polascik TJ, Eby Y, Tokino K, Califano J, Merlo A, Mao L, Herath J, Jenkins R, Westra W, Rutter JL, Buckler A, Gabrielson E, Tockman M, Cho KR, Hedrick L, Bova GS, Isaacs W, Koch W, Schwab D, Sidransky D: Frequency of homozygous deletion at p16/CDKN2 in primary human tumours. Nat Genet 11: 210-212, 1995

    Google Scholar 

  49. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943-1946, 1997

    Google Scholar 

  50. Li L, Li X, Francke U, Cohen SN: The TSG101 tumor susceptibility gene is located in chromosome 11 band p15 and is mutated in human breast cancer. Cell 88: 143-154, 1997

    Google Scholar 

  51. Zhou J, Ng AYN, Tymms MJ, Jermiin LS, Seth AK, Thomas RS, Kola I: A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13-15, a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene 17: 2719-2732, 1998

    Google Scholar 

  52. Dong J-T, Lamb PW, Rinker-Schaeffer CW, Vukanovic J, Ichikawa T, Isaacs JT, Barrett JC: KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science 268: 884-886, 1995

    Google Scholar 

  53. Hinds PW, Dowdy SF, Eaton EN, Arnold A, Weinberg RA: Function of a human cyclin gene as an oncogene. Proc Natl Acad Sci 91: 709-713, 1994

    Google Scholar 

  54. Moncur JT, Park JP, Memoli VA, Mohandas TK, Kinlaw WB: The ‘spot 14’ gene resides in the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: implications for control of tumor metabolism. Proc Natl Acad Sci USA 95: 6989-6994, 1998

    Google Scholar 

  55. Bay J-O, Uhrhammer N, Pernin D, Presneau N, Tchirkov A, Vuillaume M, Laplace V, Grancho M, Verrelle P, Hall J, Bignon Y-J: High incidence of cancer in a family segregating a mutation of the ATM gene: possible role of ATM heterozygosity in cancer. Hum Mutat 14: 485-492, 1999

    Google Scholar 

  56. Gomyo H, Arai Y, Tanigami A, Murakami Y, Hattori M, Hosoda F, Arai K, Aikawa Y, Tsuda H, Hirohashi S, Asakawa S, Shimizu N, Soeda E, Sakaki Y, Ohki M: A 2-Mb sequenceready contig map and a novel immunoglobulin superfamily gene IGSF4 in the LOH region of chromosome 11q23.2. Genomics 62: 139-146, 1999

    Google Scholar 

  57. Suetsugu S, Miki H, Takenawa T: Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex. Biochem Biophys Res Commun 260: 296-302, 1999

    Google Scholar 

  58. Hong FD, Huang H-JS, To H, Young L-JS, Oro A, Bookstein R, Lee EY-HP, Lee W-H: Structure of the human retinoblastoma gene. Proc Natl Acad Sci USA 86: 5502-5506, 1989

    Google Scholar 

  59. Martin MD, Fischbach K, Osborne CK, Mohsin SK, Allred DC, O‘Connell P: Loss of heterozygosity events impeding breast cancer metastasis contain the MTA1 gene. Cancer Res 61: 3578-3580, 2001

    Google Scholar 

  60. Berx G, Cleton-Jansen A-M, Nollet F, de Leeuw WJF, van de Vijver MJ, Cornelisse C, van Roy F: E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J 14: 6107-6115, 1995

    Google Scholar 

  61. Tsuda H, Hirohashi S: Identification of multiple breast cancers of multicentric origin by histological observations and distribution of allele loss on chromosome 16q. Cancer Res 55: 3395-3398, 1995

    Google Scholar 

  62. Stack M, Jones D, White G, Liscia DS, Venesio T, Casey G, Crichton D, Varley J, Mitchell E, Heighway J, Santibanez-Koref M: Detailed mapping and loss of heterozygosity analysis suggests a suppressor locus involved in sporadic breast cancer within a distal region of chromosome band 17p13.3. Hum Mol Genet 4: 2047-2055, 1995

    Google Scholar 

  63. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707-712, 1989

    Google Scholar 

  64. Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IMK, King CR, Liotta LA, Steeg PS: Reduced nm23/awd protein in tumour metastasis and aberrant Drosophila development. Nature 342: 177-180, 1989

    Google Scholar 

  65. Schutte M, Hruban RH, Hedrick L, Cho KR, Nadasdy GM, Weinstein CL, Bova, Isaacs WB, Cairns P, Nawroz H, Sidransky D, Casero Jr RA, Meltzer, Hahn SA, Kern SE: DPC4 gene in various tumor types. Cancer Res 56: 2527-2530, 1996

    Google Scholar 

  66. Zou Z, Anisowicz A, Hendrix MJC, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R: Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263: 526-529, 1994

    Google Scholar 

  67. Hemminki A, Markie D, Tomlinson I, Avizienyte E, Roth S, Loukola A, Bignell G, Warren W, Aminoff M, Hoglund P, Jarvinen H, Kristo P, Pelin K, Ridanpaa M, Salovaara R, Toro T, Bodmer W, Olschwang S, Olsen AS, Stratton MR, de la Chapelle A, Aaltonen LA: A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. Nature 391: 184-187, 1998

    Google Scholar 

  68. Oesterreich S, Allred DC, Mohsin SK, Zhang Q, Wong H, Lee AV, Osborne CK, O‘Connell P: High rates of loss of heterozygosity on chromosome 19p13 in human breast cancer. Br J Cancer 84: 493-498, 2000

    Google Scholar 

  69. Anzick SL, Kononen J, Walker RL, Azorsa DO, Tanner MM, Guan X-Y, Sauter G, Kallioniemi O-P, Trent JM, Meltzer PS: AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science 277: 965-968, 1997

    Google Scholar 

  70. Sen S, Zhou H, White RA: A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene 14: 2195-2200, 1997

    Google Scholar 

  71. Collins C, Rommens JM, Kowbel D, Godfrey T, Tanner M, Hwang S, Polikoff D, Nonet G, Cochran J, Myambo K, Jay KE, Froula J, Cloutier T, Kuo W-L, Yaswen P, Dairkee S, Giovanola J, Hutchinson GB, Isola J, Kallioniemi O-P, Palazzolo M, Martin C, Ericsson C, Pinkel D, Albertson D, Li W-B, Gray JW: Positional cloning of ZNF217 and NABC1: genes amplified at 20q132 and overexpressed in breast carcinoma. Proc Natl Acad Sci USA 95: 8703-8708, 1998

    Google Scholar 

  72. Gayther SA, Batley SJ, Linger L, Bannister A, Thorpe K, Chin S-F, Daigo Y, Russell P, Wilson A, Sowter HM, Delhanty JDA, Ponder BAJ, Kouzarides T, Caldas C: Mutations truncating the EP300 acetylase in human cancers. Nature Genet 24: 300-303, 2000

    Google Scholar 

  73. Wistuba II, Tomlinson GE, Behrens C, Virmani A, Geradts J, Blum JL, Minna JD, Gazdar AF: Two identical triplet sisters carrying a germline BRCA1 gene mutation acquire very similar breast cancer somatic mutations at multiple other sites throughout the Genome. Genes Chrom Cancer 28: 359-369, 2000

    Google Scholar 

  74. Utada Y, Haga S, Kajiwara T, Kasumi F, Sakamoto G, Nakamura Y, Emi M: Allelic loss at the 8p22 region as a prognostic factor in large and estrogen receptor negative breast carcinomas. Cancer 88: 1410-1416, 2000

    Google Scholar 

  75. Buerger H, Otterbach F, Simon R, Schafer KL, Poremba C, Diallo R, Brinkschmidt C, Dockhorn-Dworniczak B, Boecker W: Different genetic pathways in the evolution of invasive breast cancer are associated with distinct morphological subtypes. J Pathol 189: 521-526, 1999

    Google Scholar 

  76. Seitz S, Poppe K, Fischer J, Nothnagel A, Estevez-Schwarz L, Haensch W, Schlag PM, Scherneck S: Detailed deletion mapping in sporadic breast cancer at chromosomal region 17p13 distal to the TP53 gene: association with clinicopathological parameters. J Pathol 194: 318-326, 2001

    Google Scholar 

  77. Querzoli P, Albonico G, di Iasio MG, Ferretti S, Rinaldi R, Cariello A, Pedriali M, Matteuzzi M, Maestri I, Nenci I: Biophenotypes and survival of BRCA1 and TP53 deleted breast cancer in young women. Breast Cancer Res Treat 66: 135-142, 2001

    Google Scholar 

  78. Hermsen MA, Baak JP, Meijer GA, Weiss JM, Walboomers JW, Snijders PJ, van Diest PJ: Genetic analysis of 53 lymph node-negative breast carcinomas by CGH and relation to clinical, pathological, morphometric, and DNA cytometric prognostic factors. J Pathol 186: 356-362, 1998

    Google Scholar 

  79. Buerger H, Mommers EC, Littmann R, Simon R, Diallo R, Poremba C, Dockhorn-Dworniczak B, van Diest PJ, Boecker W: Ductal invasive G2 and G3 carcinomas of the breast are the end stages of at least two different lines of genetic evolution. J Pathol 194: 165-170, 2001

    Google Scholar 

  80. Hirano A, Emi M, Tsuneizumi M, Utada Y, Yoshimoto M, Kasumi F, Akiyama F, Sakamoto G, Haga S, Kajiwara T, Nakamura Y: Allelic losses of loci at 3p25.1, 8p22, 13q12, 17p13.3, and 22q13 correlate with postoperative recurrence in breast cancer. Clin Cancer Res 7: 876-882, 2001

    Google Scholar 

  81. Watatani M, Inui H, Nagayama K, Imanishi Y, Nishimura K, Hashimoto Y, Yamauchi E, Hojo T, Kotsuma Y, Yamato M, Matsunami N, Yasutomi M: Identification of high-risk breast cancer patients from genetic changes of their tumors. Surg Today 30: 516-522, 2000

    Google Scholar 

  82. Borg A, Zhang QX, Olsson H, Wenngren E: Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. Genes Chrom Cancer 5: 311-320, 1992

    Google Scholar 

  83. Jain AN, Chin K, Borresen-Dale AL, Erikstein BK, Eynstein Lonning P, Kaaresen R, Gray JW: Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with p53 status and patient survival. Proc Natl Acad Sci USA 98: 7952-7957, 2001

    Google Scholar 

  84. Lindblom A, Rotstein S, Skoog L, Nordenskjold M, Larsson C: Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases. Cancer Res 53: 3707-3711, 1993

    Google Scholar 

  85. Asgeirsson KS, Jonasson JG, Tryggvadottir L, Olafsdottir K, Sigurgeirsdottir JR, Ingvarsson S, Ogmundsdottir HM: Altered expression of E-cadherin in breast cancer: patterns, mechanisms and clinical significance. Eur J Cancer 36: 1098-1106, 2000

    Google Scholar 

  86. Geisler S, Lonning PE, Aas T, Johnsen H, Fluge O, Haugen DF, Lillehaug JR, Akslen LA, Borresen-Dale AL: Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res 61: 2505-2512, 2001

    Google Scholar 

  87. Hiorns LR, Seckl MJ, Paradinas F, Sharp SY, Skelton LA, Brunstrom G, Newlands ES, Kelland LR, Leyland-Jones B: A molecular cytogenetic approach to studying platinum resistance. J Inorg Biochem 77: 95-104, 1999

    Google Scholar 

  88. Hansen LL, Yilmaz M, Overgaard J, Andersen J, Kruse TA: Allelic loss of 16q23.2-24.2 is an independent marker of good prognosis in primary breast cancer. Cancer Res 58: 2166-2169, 1998

    Google Scholar 

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  1. Breast Center, Departments of Molecular and Cellular Biology, and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

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O‘Connell, P. Genetic and Cytogenetic Analyses of Breast Cancer Yield Different Perspectives of a Complex Disease. Breast Cancer Res Treat 78, 347–357 (2003). https://doi.org/10.1023/A:1023037925950

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