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Principles of Molecular Oncology pp 151–179Cite as

Genetic Markers in Breast Tumors with Hereditary Predisposition

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Abstract

Over the past two decades, we have come to an understanding of cancer as a genetic disorder caused by the progressive accumulation of multiple genetic changes, which include point mutations, chromosomal rearrangements, viral insertions, and genomic amplifications and deletions (1,2). Gene amplifications, point mutations, viral insertions, and chromosomal rearrangements are dominant genetic damages that primarily target oncogenes whose gain of function (overexpression) leads to dysregulation of cell growth and transformation. Recessive point mutations and deletions mainly cause loss of function in tumor suppressor genes (TSGs) that control cell-cycle progression and DNA repair mechanisms (2).

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References

  1. Bishop JM. The molecular genetics of cancer. Science. 1987; 235: 305–311.

    Article  PubMed  CAS  Google Scholar 

  2. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998; 396: 643–649.

    Article  PubMed  CAS  Google Scholar 

  3. Nathanson KL, Wooster R, Weber BL, Nathanson KL. Breast cancer genetics: what we know and what we need. Nat Med. 2001; 7: 552–556.

    Article  PubMed  CAS  Google Scholar 

  4. Couch FJ, DeShano ML, Blackwood MA, et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med. 1997; 336: 1409–1415.

    Article  PubMed  CAS  Google Scholar 

  5. Couch FJ, Weber BL. Breast Cancer. In: Genetic Basis of Human Cancer. ( Vogelstein B, Kinzler KW, eds.) McGraw-Hill, New York, NY, 1998; pp. 537–551.

    Google Scholar 

  6. Bertwistle D, Ashworth A. Functions of the BRCA1 and BRCA2 genes. Curr Opin Genet Dev. 1998; 8: 14–20.

    Article  PubMed  CAS  Google Scholar 

  7. Welcsh PL, Schubert EL, King MC. Inherited breast cancer: an emerging picture. Clin Genet. 1998; 54: 447–458.

    Article  PubMed  CAS  Google Scholar 

  8. Irminger-Finger I, Siegel BD, Leung WC. The functions of breast cancer susceptibility gene 1 (BRCA1) product and its associated proteins. Biol Chem. 1999; 380: 117–128.

    Article  PubMed  CAS  Google Scholar 

  9. Deng CX, Brodie SG. Roles of BRCA1 and its interacting proteins. Bioessays. 2000; 22: 728–737.

    Article  PubMed  CAS  Google Scholar 

  10. Scully R. Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res. 2000; 2: 324–330.

    Article  PubMed  CAS  Google Scholar 

  11. Arver B, Du Q, Chen J, Luo L, Lindblom A. Hereditary breast cancer: a review. Semin Cancer Biol. 2000; 10: 271–288.

    Article  PubMed  CAS  Google Scholar 

  12. Zheng L, Li S, Boyer TG, Lee WH. Lessons learned from BRCA1 and BRCA2. Oncogene. 2000; 19: 6159–6175.

    Article  PubMed  CAS  Google Scholar 

  13. Venkitaraman AR. Functions of BRCA1 and BRCA2 in the biological response to DNA damage. J Cell Sci. 2001; 114: 3591–3598.

    PubMed  CAS  Google Scholar 

  14. Venkitaraman AR. Chromosome stability, DNA recombination and the BRCA2 tumour suppressor. Curr Opin Cell Biol. 2001; 13: 338–343.

    Article  PubMed  CAS  Google Scholar 

  15. Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002; 108: 171–182.

    Article  PubMed  CAS  Google Scholar 

  16. Scully R, Puget N. BRCA1 and BRCA2 in hereditary breast cancer. Biochimie. 2002; 84: 95–102.

    Article  PubMed  CAS  Google Scholar 

  17. Jasin M. Homologous repair of DNA damage and tumorigenesis: the BRCA connection. Oncogene. 2002; 21: 8981–8993.

    Article  PubMed  CAS  Google Scholar 

  18. Miki Y, Swensen J, Shattuck-Eidens D, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994; 266: 66–71.

    Article  PubMed  CAS  Google Scholar 

  19. Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995; 378: 789–792.

    Article  PubMed  CAS  Google Scholar 

  20. Tavtigian SV, Simard J, Rommens J, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 1996; 12: 333–337.

    Article  PubMed  CAS  Google Scholar 

  21. Osorio A, de la Hoya M, Rodriguez-Lopez R, et al. Loss of heterozygosity analysis at the BRCA loci in tumor samples from patients with familial breast cancer. Int J Cancer. 2002; 99: 305–309.

    Article  PubMed  CAS  Google Scholar 

  22. Eiriksdottir G, Barkardottir RB, Agnarsson BA, et al. High incidence of loss of heterozygosity at chromosome 17p13 in breast tumours from BRCA2 mutation carriers. Oncogene. 1998; 16: 21–26.

    Article  PubMed  CAS  Google Scholar 

  23. Kinzler KW, Vogelstein B. Cancer-susceptibility genes: gatekeepers and caretakers. Nature. 1997; 386: 761, 763.

    Google Scholar 

  24. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998; 62: 676–689.

    Article  PubMed  CAS  Google Scholar 

  25. Deng CX, Scott F. Role of the tumor suppressor gene Brca1 in genetic stability and mammary gland tumor formation. Oncogene. 2000; 19: 1059–1064.

    Article  PubMed  CAS  Google Scholar 

  26. Jacquemier J, Eisinger F, Birnbaum D, Sobol H. Histoprognostic grade in BRCA 1 -associated breast cancer. Lancet. 1995; 345: 1503.

    Article  PubMed  CAS  Google Scholar 

  27. Breast Cancer Linkage Consortium. Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet. 1997; 349: 1505–1510.

    Google Scholar 

  28. Osin P, Gusterson BA, Philp E, et al. Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. Eur J Cancer. 1998; 34: 1683–1686.

    Article  PubMed  CAS  Google Scholar 

  29. Lakhani SR, Jacquemier J, Sloane JP, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998; 90: 1138–1145.

    Article  PubMed  CAS  Google Scholar 

  30. Eisinger F, Jacquemier J, Nogues C, Birnbaum D, Sobol H. Steroid receptors in hereditary breast carcinomas associated with BRCA1 or BRCA2 mutations or unknown susceptibility genes. Cancer. 1999; 85: 2291–2295.

    Article  PubMed  CAS  Google Scholar 

  31. Armes JE, Trute L, White D, et al. Distinct molecular pathogeneses of early-onset breast cancers in BRCA1 and BRCA2 mutation carriers: a population-based study. Cancer Res. 1999; 59: 2011–2017.

    PubMed  CAS  Google Scholar 

  32. Osin PP, Lakhani SR. The pathology of familial breast cancer: immunohistochemistry and molecular analysis. Breast Cancer Res. 1999; 1: 36–40.

    Article  PubMed  CAS  Google Scholar 

  33. Chappuis PO, Nethercot V, Foulkes WD. Clinico-pathological characteristics of BRCA1- and BRCA2-related breast cancer. Semin Surg Oncol. 2000; 18: 287–295.

    Article  PubMed  CAS  Google Scholar 

  34. Phillips KA. Immunophenotypic and pathologic differences between BRCA1 and BRCA2 hereditary breast cancers. J Clin Oncol. 2000; 18: 107S–112S.

    PubMed  CAS  Google Scholar 

  35. Agnarsson BA, Jonasson JG, Bjornsdottir IB, Barkardottir RB, Egilsson V, Sigurdsson H. Inherited BRCA2 mutation associated with high grade breast cancer. Breast Cancer Res. Treat 1998; 47: 121–127.

    Article  PubMed  CAS  Google Scholar 

  36. Lakhani SR, Van De Vijver MJ, Jacquemier J, et al. The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol. 2002; 20: 2310–2318.

    Article  PubMed  CAS  Google Scholar 

  37. Marcus JN, Watson P, Page DL, et al. BRCA2 hereditary breast cancer pathophenotype. Breast Cancer Res. Treat 1997; 44: 275–277.

    CAS  Google Scholar 

  38. Verhoog LC, Berns EM, Brekelmans CT, Seynaeve C, Meijers-Heijboer EJ, Klijn JG. Prognostic significance of germline BRCA2 mutations in hereditary breast cancer patients. J Clin Oncol. 2000; 18: 119S–224S.

    PubMed  CAS  Google Scholar 

  39. Hollander MC, Fornace AJ Jr. Genomic instability, centrosome amplification, cell cycle checkpoints and Gadd45a. Oncogene. 2002; 21: 6228–633.

    Article  PubMed  CAS  Google Scholar 

  40. Marcus JN, Watson P, Page DL, et al. Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer. 1996; 77: 697–709.

    Article  PubMed  CAS  Google Scholar 

  41. Tirkkonen M, Johannsson O, Agnarsson BA, et al. Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations. Cancer Res. 1997; 57: 1222–1227.

    PubMed  CAS  Google Scholar 

  42. Johannsson OT, Idvall I, Anderson C, et al. Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer. 1997; 33: 362–371.

    Article  PubMed  CAS  Google Scholar 

  43. Gretarsdottir S, Thorlacius S, Valgardsdottir R, et al. BRCA2 and p53 mutations in primary breast cancer in relation to genetic instability. Cancer Res. 1998; 58: 859–862.

    PubMed  CAS  Google Scholar 

  44. Tomlinson GE, Chen TT, Stastny VA, et al. Characterization of a breast cancer cell line derived from a germ-line BRCA1 mutation carrier. Cancer Res. 1998; 58: 3237–3242.

    PubMed  CAS  Google Scholar 

  45. Tirkkonen M, Kainu T, Loman N, et al. Somatic genetic alterations in BRCA2-associated and sporadic male breast cancer. Genes Chrom Cancer 1999; 24: 56–61.

    Article  PubMed  CAS  Google Scholar 

  46. Lodewyk FA, Wessels LF, van Welsem T, van’t Veer LJ, Reinders, MJ, Nederlof PM. Molecular classification of breast carcinomas by comparative genomic hybridization: a specific somatic genetic profile for BRCA1 tumors. Cancer Res. 2002; 62: 7110–7117.

    Google Scholar 

  47. Nathanson KL, Shugart YY, Omaruddin R, et al. CGH-targeted linkage analysis reveals a possible BRCA1 modifier locus on chromosome 5q. Hum Mol Genet 2002; 11: 1327–1332.

    Article  PubMed  CAS  Google Scholar 

  48. Reimer CL, Borras AM, Kurdistani SK, et al. Altered regulation of cyclin G in human breast cancer and its specific localization at replication foci in response to DNA damage in p53+/+ cells. J Biol Chem. 1999; 274:11, 022–11, 029.

    Google Scholar 

  49. Savelyeva L, Claas A, Gier S, et al. An interstitial tandem duplication of 9p23–24 coexists with a mutation in the BRCA2 gene in the germ line of three brothers with breast cancer. Cancer Res. 1998; 58: 863–866.

    PubMed  CAS  Google Scholar 

  50. Savelyeva L, Claas A, Matzner I, et al. Constitutional genomic instability with inversions, duplications, and amplifications in 9p23–24 in BRCA2 mutation carriers. Cancer Res. 2001; 61: 5179–5185.

    PubMed  CAS  Google Scholar 

  51. Xu X, Weaver Z, Linke SP, et al. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. Mol Cell. 1999; 3: 389–395.

    Article  PubMed  CAS  Google Scholar 

  52. Weaver Z, Montagna C, Xu X, et al. Mammary tumors in mice conditionally mutant for Brca1 exhibit gross genomic instability and centrosome amplification yet display a recurring distribution of genomic imbalances that is similar to human breast cancer. Oncogene. 2002; 21: 5097–5107.

    Article  PubMed  CAS  Google Scholar 

  53. Tutt A, Gabriel A, Bertwistle D, et al. Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification. Curr Biol. 1999; 9: 1107–1110.

    Article  PubMed  CAS  Google Scholar 

  54. Hsu LC, White RL. BRCA1 is associated with the centrosome during mitosis. Proc Natl Acad Sci USA. 1998; 95:12, 983–12, 988.

    Google Scholar 

  55. Hu YF, Hao ZL, Li R. Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. Genes Dev. 1999; 13: 637–642.

    Article  PubMed  CAS  Google Scholar 

  56. Hsu LC, Doan TP, White RL. Identification of a gamma-tubulin-binding domain in BRCA1. Cancer Res. 2001; 61: 7713–7718.

    PubMed  CAS  Google Scholar 

  57. Lingle WL, Barrett SL, Negron VC, et al. Centrosome amplification drives chromosomal instability in breast tumor development. Proc Natl Acad Sci USA. 2002; 99: 1978–1983.

    Article  PubMed  CAS  Google Scholar 

  58. D’Assoro AB, Lingle WL, Salisbury JL. Centrosome amplification and the development of cancer. Oncogene. 2002; 21: 6146–6153.

    Article  PubMed  CAS  Google Scholar 

  59. Wallace-Brodeur RR, Lowe SW. Clinical implications of p53 mutations. Cell Mol Life Sci? 1999; 55: 64–75.

    Article  PubMed  CAS  Google Scholar 

  60. Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA. p53 mutations in BRCA1- associated familial breast cancer. Lancet. 1997; 350: 638–639.

    Article  PubMed  CAS  Google Scholar 

  61. Crook T, Brooks LA, Crossland S, et al. p53 mutation with frequent novel condons but not a mutator phenotype in BRCA1- and BRCA2-associated breast tumours. Oncogene. 1998; 17: 1681–1689.

    Article  PubMed  CAS  Google Scholar 

  62. Sobol H, Eisinger F, Sauvan R, Noguchi T, Jacquemier J, Birnbaum D. [Impact of recent oncogenetic progress on the management of high risk breast cancer patients: the example of BRCA1 and BRCA2 genes]. Ann Endocrinol (Paris). 1998; 59: 459–464.

    CAS  Google Scholar 

  63. Lynch BJ, Holden JA, Buys SS, Neuhausen SL, Gaffney DK. Pathobiologic characteristics of hereditary breast cancer. Hum Pathol. 1998; 29: 1140–1144.

    Article  PubMed  CAS  Google Scholar 

  64. Greenblatt MS, Chappuis PO, Bond JP, Hamel N, Foulkes WD. TP53 mutations in breast cancer associated with BRCA1 or BRCA2 germ-line mutations: distinctive spectrum and structural distribution. Cancer Res. 2001; 61: 4092–4097.

    PubMed  CAS  Google Scholar 

  65. Schuyer M, Berns EM. Is TP53 dysfunction required for BRCA1-associated carcinogenesis? Mol Cell Endocrinol. 1999; 155: 143–152.

    Article  PubMed  CAS  Google Scholar 

  66. Robson M, Rajan P, Rosen PP, et al. BRCA-associated breast cancer: absence of a characteristic immunophenotype. Cancer Res. 1998; 58: 1839–1842.

    PubMed  CAS  Google Scholar 

  67. Noguchi S, Kasugai T, Miki Y, Fukutomi T, Emi M, Nomizu T. Clinicopathologic analysis of BRCA1- or BRCA2-associated hereditary breast carcinoma in Japanese women. Cancer. 1999; 85: 2200–2205.

    Article  PubMed  CAS  Google Scholar 

  68. de Cremoux P, Salomon AV, Liva S, et al. p53 mutation as a genetic trait of typical medullary breast carcinoma. J Natl Cancer Inst. 1999; 91: 641–643.

    Article  PubMed  Google Scholar 

  69. Eisinger F, Jacquemier J, Charpin C, et al. Mutations at BRCA1: the medullary breast carcinoma revisited. Cancer Res. 1998; 58: 1588–1592.

    PubMed  CAS  Google Scholar 

  70. Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H. BRCA1 regulates p53-dependent gene expression. Proc Natl Acad Sci USA. 1998; 95: 2302–2306.

    Article  PubMed  CAS  Google Scholar 

  71. Zhang H, Somasundaram K, Peng Y, et al. BRCA1 physically associates with p53 and stimulates its transcriptional activity. Oncogene. 1998; 16: 1713–1721.

    Article  PubMed  CAS  Google Scholar 

  72. Marmorstein LY, Ouchi T, Aaronson SA. The BRCA2 gene product functionally interacts with p53 and RAD51. Proc Natl Acad Sci USA. 1998; 95:13, 869–13, 874.

    Google Scholar 

  73. Offit K. Are BRCA1- and BRCA2-associated breast cancers different? J Clin Oncol. 2000; 18: 104S–106S.

    PubMed  CAS  Google Scholar 

  74. Xu X, Wagner KU, Larson D, et al. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet. 1999; 22: 37–43.

    Article  PubMed  CAS  Google Scholar 

  75. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet. 2001; 29: 418–425.

    Article  PubMed  CAS  Google Scholar 

  76. Moynahan ME. The cancer connection: BRCA1 and BRCA2 tumor suppression in mice and humans. Oncogene. 2002; 21: 8994–9007.

    Article  PubMed  CAS  Google Scholar 

  77. Elledge RM, Allred DC. The p53 tumor suppressor gene in breast cancer. Breast Cancer Res Treat. 1994; 32: 39–47.

    Article  PubMed  CAS  Google Scholar 

  78. Hakem R, de la Pompa JL, Elia A, Potter J, Mak TW. Partial rescue of Brca1 (5–6) early embryonic lethality by p53 or p21 null mutation. Nat Genet. 1997; 16: 298–302.

    Article  PubMed  CAS  Google Scholar 

  79. Berx G, Cleton-Jansen AM, Strumane K, et al. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene. 1996; 13: 1919–1925.

    PubMed  CAS  Google Scholar 

  80. De Leeuw WJ, Berx G, Vos CB, et al. Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol. 1997; 183: 404–411.

    Article  PubMed  Google Scholar 

  81. Salahshor S, Haixin L, Huo H, et al. Low frequency of E-cadherin alterations in familial breast cancer. Breast Cancer Res. 2001; 3: 199–207.

    Article  PubMed  CAS  Google Scholar 

  82. Vaziri SA, Krumroy LM, Elson P, et al. Breast tumor immunophenotype of BRCA 1-mutation carriers is influenced by age at diagnosis. Clin Cancer Res. 2001; 7: 1937–1945.

    PubMed  CAS  Google Scholar 

  83. Kauraniemi P, Hedenfalk I, Persson K, et al. MYB oncogene amplification in hereditary BRCA1 breast cancer. Cancer Res. 2000; 60: 5323–5328.

    PubMed  CAS  Google Scholar 

  84. Weston K. Myb proteins in life, death and differentiation. Curr Opin Genet Dev. 1998; 8: 76–81.

    Article  PubMed  CAS  Google Scholar 

  85. Oh IH, Reddy EP. The myb gene family in cell growth, differentiation and apoptosis. Oncogene. 1999; 18: 3017–3033.

    Article  PubMed  CAS  Google Scholar 

  86. Ness SA. The Myb oncoprotein: regulating a regulator. Biochim Biophys Acta. 1996; 1288: F123–F139.

    PubMed  CAS  Google Scholar 

  87. Funato T, Satou J, Kozawa K, Fujimaki S, Miura T, Kaku M. Use of c-myb antisense oligonucleotides to increase the sensitivity of human colon cancer cells to cisplatin. Oncol Rep. 2001; 8: 807–810.

    PubMed  CAS  Google Scholar 

  88. Toscani A, Mettus RV, Coupland R, et al. Arrest of spermatogenesis and defective breast development in mice lacking A-myb. Nature. 1997; 386: 713–717.

    Article  PubMed  CAS  Google Scholar 

  89. Guerin M, Barrois M, Riou G. [The expression of c-myb is strongly associated with the presence of estrogen and progesterone receptors in breast cancer]. CR Acad Sci III. 1988; 307: 855–861.

    CAS  Google Scholar 

  90. Guerin M, Sheng ZM, Andrieu N, Riou G. Strong association between c-myb and oestrogen-receptor expression in human breast cancer. Oncogene. 1990; 5: 131–135.

    PubMed  CAS  Google Scholar 

  91. Barlund M, Nupponen NN, Karhu R, et al. Molecular cytogenetic mapping of 24 CEPH YACs and 24 gene-specific large insert probes to chromosome 17. Cytogenet Cell Genet. 1998; 82: 189–191.

    Article  PubMed  CAS  Google Scholar 

  92. Jacobs JJ, Keblusek P, Robanus-Maandag E, et al. Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers. Nat Genet. 2000; 26: 291–299.

    Article  PubMed  CAS  Google Scholar 

  93. Erson AE, Niell BL, DeMers SK, Rouillard JM, Hanash SM, Petty EM. Overexpressed genes/ ESTs and characterization of distinct amplicons on 17q23 in breast cancer cells. Neoplasia. 2001; 3: 521–526.

    Article  PubMed  CAS  Google Scholar 

  94. Rouillard JM, Erson AE, Kuick R, et al. Virtual genome scan: a tool for restriction landmark-based scanning of the human genome. Genome Res. 2001; 11: 1453–1459.

    Article  PubMed  CAS  Google Scholar 

  95. Wu G, Sinclair C, Hinson S, Ingle JN, Roche PC, Couch FJ. Structural analysis of the 17q22– 23 amplicon identifies several independent targets of amplification in breast cancer cell lines and tumors. Cancer Res. 2001; 61: 4951–4955.

    PubMed  CAS  Google Scholar 

  96. Mahlamaki EH, Barlund M, Tanner M, et al. Frequent amplification of 8q24, 1 1q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chrom Cancer 2002; 35: 353–358.

    Article  PubMed  CAS  Google Scholar 

  97. Sinclair CS, Adem C, Naderi A, et al. TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors. Cancer Res. 2002; 62: 3587–3591.

    PubMed  CAS  Google Scholar 

  98. Papaioannou VE. T-box family reunion. Trends Genet. 1997; 13: 212–213.

    Article  PubMed  CAS  Google Scholar 

  99. Carlson H, Ota S, Song Y, Chen Y, Hurlin PJ. Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation. Oncogene. 2002; 21: 3827–3835.

    Article  PubMed  CAS  Google Scholar 

  100. Lingbeek ME, Jacobs JJ, van Lohuizen M. The T-box repressors TBX2 and TBX3 specifically regulate the tumor suppressor gene p14ARF via a variant T-site in the initiator. J Biol Chem. 2002; 277:26, 120–26, 127.

    Google Scholar 

  101. Croce CM. Molecular biology of lymphomas. Semin Oncol. 1993; 20: 31–46.

    PubMed  CAS  Google Scholar 

  102. Liao DJ, Dickson RB. c-Myc in breast cancer. Endocr Relat Cancer. 2000; 7: 143–164.

    Article  PubMed  CAS  Google Scholar 

  103. Zajac-Kaye M. Myc oncogene: a key component in cell cycle regulation and its implication for lung cancer. Lung Cancer. 2001; 34 (Suppl. 2): S43–S46.

    Article  PubMed  Google Scholar 

  104. Grushko TA, Das S, Schumm P, et al. C-MYC amplification is a feature of BRCA1-associated hereditary and BRCA1-methylated sporadic breast cancers, 41st American Society for Cell Biology Annual Meeting, December 8–12, Washington, DC, 2001. Mol Biol Cell. 2001; 12:S: 13a.

    Google Scholar 

  105. Olopade OI, Grushko TA, Hagos F, et al. BRCA1-associated tumors have a distinct molecular pathogenesis. In: The Department of Defense Breast Cancer Research Program’s 2002 Era of Hope Proceedings, Era of Hope Department of Defense Breast Cancer Research Meeting, Hosted by U.S. Army Medical Research and Materiel Command. Orlando, FL, September 25–28, 2002; vol. III, pp. 43–49.

    Google Scholar 

  106. Hedenfalk I, Duggan D, Chen Y, et al. Gene-expression profiles in hereditary breast cancer. N Engl J Med. 2001; 344: 539–548.

    Article  PubMed  CAS  Google Scholar 

  107. van t‘Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002; 415:530–536.

    Google Scholar 

  108. Brodie SG, Xu X, Qiao W, Li WM, Cao L, Deng CX. Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice. Oncogene. 2001; 20: 7514–7523.

    Article  PubMed  CAS  Google Scholar 

  109. Wang Q, Zhang H, Kajino K, Greene MI. BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells. Oncogene. 1998; 17: 1939–1948.

    Article  PubMed  CAS  Google Scholar 

  110. Li H, Lee TH, Avraham H. A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Mycinduced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer. J Biol Chem. 2002; 277:20, 965–20, 973.

    Google Scholar 

  111. Penn LJ, Laufer EM, Land H. C-MYC: evidence for multiple regulatory functions. Semin Cancer Biol. 1990; 1: 69–80.

    PubMed  CAS  Google Scholar 

  112. Sivak LE, Tai KF, Smith RS, Dillon PA, Brodeur GM, Carroll WL. Autoregulation of the human N-myc oncogene is disrupted in amplified but not single-copy neuroblastoma cell lines. Oncogene. 1997; 15: 1937–1946.

    Article  PubMed  CAS  Google Scholar 

  113. Hung MC, Lau YK. Basic science of HER-2/neu: a review. Semin Oncol. 1999; 26: 51–59.

    PubMed  CAS  Google Scholar 

  114. Revillion F, Bonneterre J, Peyrat JP. ERBB2 oncogene in human breast cancer and its clinical significance. Eur J Cancer. 1998; 34: 791–808.

    Article  PubMed  CAS  Google Scholar 

  115. Pegram MD, Pauletti G, Slamon DJ. HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat. 1998; 52: 65–77.

    Article  PubMed  CAS  Google Scholar 

  116. Ross JS, Fletcher JA. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells. 1998; 16: 413–428.

    Article  PubMed  CAS  Google Scholar 

  117. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344: 783–792.

    Article  PubMed  CAS  Google Scholar 

  118. Grushko TA, Blackwood MA, Schumm PL, et al. Molecular-cytogenetic analysis of HER-2/ neu gene in BRCA 1 -associated breast cancers. Cancer Res. 2002; 62: 1481–1488.

    PubMed  CAS  Google Scholar 

  119. Persons DL, Borelli KA, Hsu PH. Quantitation of HER-2/neu and c-myc gene amplification in breast carcinoma using fluorescence in situ hybridization. Mod Pathol. 1997; 10: 720–727.

    PubMed  CAS  Google Scholar 

  120. Gancberg D, Lespagnard L, Rouas G, et al. Sensitivity of HER-2/neu antibodies in archival tissue samples of invasive breast carcinomas. Correlation with oncogene amplification in 160 cases. Am J Clin Pathol. 2000; 113: 675–682.

    Article  PubMed  CAS  Google Scholar 

  121. Isola J, Chu L, DeVries S, et al. Genetic alterations in ERBB2-amplified breast carcinomas. Clin Cancer Res. 1999; 5: 4140–145.

    PubMed  CAS  Google Scholar 

  122. Ruas M, Peters G. The p16INK4a/CDKN2A tumor suppressor and its relatives. Biochim Biophys Acta. 1998; 1378: F115–F177.

    PubMed  CAS  Google Scholar 

  123. Borg A, Sandberg T, Nilsson K, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J Natl Cancer Inst. 2000; 92: 1260–1266.

    Article  PubMed  CAS  Google Scholar 

  124. Kamb A. Role of a cell cycle regulator in hereditary and sporadic cancer. Cold Spring Harb Symp Quant Biol. 1994; 59: 39–47.

    Article  PubMed  CAS  Google Scholar 

  125. Xu L, Sgroi D, Sterner CJ, et al. Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas. Cancer Res. 1994; 54: 5262–5264.

    PubMed  CAS  Google Scholar 

  126. Quesnel B, Fenaux P, Philippe N, et al. Analysis of p16 gene deletion and point mutation in breast carcinoma. Br J Cancer. 1995; 72: 351–353.

    Article  PubMed  CAS  Google Scholar 

  127. Esteller M, Fraga MF, Guo M, et al. DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet. 2001; 10: 3001–3007.

    Article  PubMed  CAS  Google Scholar 

  128. Elledge RM, Allred DC. Prognostic and predictive value of p53 and p21 in breast cancer. Breast Cancer Res Treat. 1998; 52: 79–98.

    Article  PubMed  CAS  Google Scholar 

  129. el-Deiry WS, Harper JW, O’Connor PM, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res. 1994; 54: 1169–1174.

    PubMed  CAS  Google Scholar 

  130. Polyak K, Kato JY, Solomon MJ, et al. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 1994; 8: 9–22.

    Article  PubMed  CAS  Google Scholar 

  131. Bloom J, Pagano M. Deregulated degradation of the cdk inhibitor p27 and malignant transformation. Semin Cancer Biol. 2003; 13: 41–47.

    Article  PubMed  CAS  Google Scholar 

  132. Tan P, Cady B, Wanner M, et al. The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 1997; 57: 1259–1263.

    PubMed  CAS  Google Scholar 

  133. Elstner E, Williamson EA, Zang C, et al. Novel therapeutic approach: ligands for PPARgamma and retinoid receptors induce apoptosis in bcl-2-positive human breast cancer cells. Breast Cancer Res Treat. 2002; 74: 155–165.

    Article  PubMed  CAS  Google Scholar 

  134. Williamson EA, Dadmanesh F, Koeffler HP. BRCA1 transactivates the cyclin-dependent kinase inhibitor p27(Kip1). Oncogene. 2002; 21: 3199–3206.

    Article  PubMed  CAS  Google Scholar 

  135. Yang W, Shen J, Wu M, et al. Repression of transcription of the p27(Kip1) cyclin-dependent kinase inhibitor gene by c-Myc. Oncogene. 2001; 20: 1688–1702.

    Article  PubMed  CAS  Google Scholar 

  136. Liang J, Zubovitz J, Petrocelli T, et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med. 2002; 8: 1153–1160.

    Article  PubMed  CAS  Google Scholar 

  137. Shin I, Yakes FM, Rojo F, et al. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat Med. 2002; 8: 1145–1152.

    Article  PubMed  CAS  Google Scholar 

  138. Viglietto G, Motti ML, Bruni P, et al. Cytoplasmic relocalization and inhibition of the cyclindependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat Med. 2002; 8: 1136–1144.

    Article  PubMed  CAS  Google Scholar 

  139. Freneaux P, Stoppa-Lyonnet D, Mouret E, et al. Low expression of bcl-2 in Brca1 -associated breast cancers. Br J Cancer. 2000; 83: 1318–1322.

    Article  PubMed  CAS  Google Scholar 

  140. de Bock GH, Tollenaar RA, Papelard H, Cornelisse CJ, Devilee P, van de Vijver MJ. Clinical and pathological features of BRCA1 associated carcinomas in a hospital-based sample of Dutch breast cancer patients. Br J Cancer. 2001; 85: 1347–1350.

    Article  PubMed  Google Scholar 

  141. Vaziri SA, Tubbs RR, Darlington G, Casey G. Absence of CCND1 gene amplification in breast tumours of BRCA1 mutation carriers. Mol Pathol. 2001; 54: 259–263.

    Article  PubMed  CAS  Google Scholar 

  142. Barnes DM, Gillett CE. Cyclin D1 in breast cancer. Breast Cancer Res Treat. 1998; 52: 1–15.

    Article  PubMed  CAS  Google Scholar 

  143. Keyomarsi K, O’Leary N, Molnar G, Lees E, Fingert HJ, Pardee AB. Cyclin E, a potential prognostic marker for breast cancer. Cancer Res. 1994; 54: 380–385.

    PubMed  CAS  Google Scholar 

  144. Patel KJ, Yu VP, Lee H, et al. Involvement of Brca2 in DNA repair. Mol Cell. 1998; 1: 347–357.

    Article  PubMed  CAS  Google Scholar 

  145. Lee H, Trainer AH, Friedman LS, et al. Mitotic checkpoint inactivation fosters transformation in cells lacking the breast cancer susceptibility gene, Brca2. Mol Cell. 1999; 4: 1–10.

    Article  PubMed  CAS  Google Scholar 

  146. Malzahn K, Mitze M, Thoenes M, Moll R. Biological and prognostic significance of stratified epithelial cytokeratins in infiltrating ductal breast carcinomas. Virchows Arch. 1998; 433: 119–129.

    Article  PubMed  CAS  Google Scholar 

  147. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000; 406: 747–752.

    Article  PubMed  CAS  Google Scholar 

  148. Sorlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001; 98: 10, 869–10, 874.

    Google Scholar 

  149. Olopade OI, Grushko T. Gene-expression profiles in hereditary breast cancer. N Engl J Med. 2001; 344: 2028–2029.

    Article  PubMed  CAS  Google Scholar 

  150. Fulco RA, Petix M, Salimbeni V, Torre EA. Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer. Minerva Med. 1998; 89: 5–10.

    PubMed  CAS  Google Scholar 

  151. Rebbeck TR. Inherited predisposition and breast cancer: modifiers of BRCA1/2-associated breast cancer risk. Environ Mol Mutagen. 2002; 39: 228–234.

    Article  PubMed  CAS  Google Scholar 

  152. Rebbeck TR, Wang Y, Kantoff PW, et al. Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Res. 2001; 61: 5420–5424.

    PubMed  CAS  Google Scholar 

  153. Gudas JM, Nguyen H, Li T, Cowan KH. Hormone-dependent regulation of BRCA1 in human breast cancer cells. Cancer Res. 1995; 55: 4561–4565.

    PubMed  CAS  Google Scholar 

  154. Marks JR, Huper G, Vaughn JP, et al. BRCA1 expression is not directly responsive to estrogen. Oncogene. 1997; 14: 115–121.

    Article  PubMed  CAS  Google Scholar 

  155. Hilakivi-Clarke L. Estrogens, BRCA1, and breast cancer. Cancer Res. 2000; 60: 4993–5001.

    PubMed  CAS  Google Scholar 

  156. van de Vijver MJ, He YD, van’t Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002; 347: 1999–2009.

    Article  PubMed  Google Scholar 

  157. Esteller M, Herman JG. Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 2002; 196: 1–7.

    Article  PubMed  CAS  Google Scholar 

  158. Collins N, Wooster R, Stratton MR. Absence of methylation of CpG dinucleotides within the promoter of the breast cancer susceptibility gene BRCA2 in normal tissues and in breast and ovarian cancers. Br J Cancer. 1997; 76: 1150–1156.

    Article  PubMed  CAS  Google Scholar 

  159. Esteller M, Corn PG, Baylin SB, Herman JG. A gene hypermethylation profile of human cancer. Cancer Res. 2001; 61: 3225–3229.

    PubMed  CAS  Google Scholar 

  160. Baylin SB, Esteller M, Rountree MR, Bachman KE, Schuebel K, Herman JG. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet. 2001; 10: 687–692.

    Article  PubMed  CAS  Google Scholar 

  161. Tesoriero A, Andersen C, Southey M, et al. De novo BRCA1 mutation in a patient with breast cancer and an inherited BRCA2 mutation. Am J Hum Genet. 1999; 65: 567–569.

    Article  PubMed  CAS  Google Scholar 

  162. Jones KA, Brown MA, Solomon E. Molecular genetics of sporadic and familial breast cancer. Cancer Surv. 1995; 25: 315–334.

    PubMed  CAS  Google Scholar 

  163. Chappuis PO, Kapusta L, Begin LR, et al. Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol. 2000; 18: 4045–4052.

    PubMed  CAS  Google Scholar 

  164. Loman N, Johannsson O, Bendahl PO, Borg A, Ferno M, Olsson H. Steroid receptors in hereditary breast carcinomas associated with BRCA1 or BRCA2 mutations or unknown susceptibility genes. Cancer. 1998; 83: 310–319.

    Article  PubMed  CAS  Google Scholar 

  165. Verhoog LC, Brekelmans CT, Seynaeve C, et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol. 1999; 17: 3396–3402.

    PubMed  CAS  Google Scholar 

  166. Lakhani SR, Gusterson BA, Jacquemier J, et al. The pathology of familial breast cancer: histological features of cancers in families not attributable to mutations in BRCA1 or BRCA2. Clin Cancer Res. 2000; 6: 782–789.

    PubMed  CAS  Google Scholar 

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Authors
  1. Tatyana A. Grushko
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  2. Olufunmilayo I. Olopade
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Editors and Affiliations

  1. Division of Medical Oncology, Hospital General de Granollers, Barcelona, Spain

    Miguel H. Bronchud MD, PhD

  2. Amgen Inc., Thousand Oaks, CA, USA

    MaryAnn Foote PhD

  3. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

    Giuseppe Giaccone MD, PhD

  4. Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Olufunmilayo I. Olopade MBBS

  5. Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research and Royal Marsden Hospital, Sutton, Surrey, UK

    Paul Workman PhD, FMedSci

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Grushko, T.A., Olopade, O.I. (2004). Genetic Markers in Breast Tumors with Hereditary Predisposition. In: Bronchud, M.H., Foote, M., Giaccone, G., Olopade, O.I., Workman, P. (eds) Principles of Molecular Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-664-5_4

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  • DOI: https://doi.org/10.1007/978-1-59259-664-5_4

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-6276-1

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