Skip to main content
SpringerLink
Log in

BRCA1 and BRCA2 Testing in Inherited Breast Cancer

  • Chapter
  • First Online:
Molecular Diagnostics

Part of the book series: Molecular and Translational Medicine ((MOLEMED))

  • 2138 Accesses

Abstract

Although breast cancer is most common in more-developed countries, it is a global problem, comprising 22.9 % of all cancers in women, excluding noninvasive skin cancers, and 13.7 % of all cancer deaths in women [1]. Excluding non-melanoma skin cancers, breast cancer is the most common cancer in women and the most common cause of cancer death in women worldwide. The USA has the world’s highest annual incidence of breast cancer. Estimates for 2011 are for the diagnosis of 232,620 new cases and 39,900 deaths [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. International Agency for Research on Cancer. World cancer report. 2008. http://www.iarc.fr/en/publications/pdfs-online/wcr/. Accessed 30 Aug 2011.

  2. American Cancer Society. Cancer facts & figures 2011. 2011. http://www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2011. Accessed 30 Aug 2011.

  3. Metcalfe KA, Finch A, Poll A, et al. Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation. Br J Cancer. 2009;100:421–5.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–92.

    Article  PubMed  CAS  Google Scholar 

  6. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77:2318–24.

    Article  PubMed  CAS  Google Scholar 

  7. Petrucelli N, Daly MB, Feldman GL. GeneReviews: BRCA1 and BRCA2 hereditary breast and ovarian cancer. 2011. http://www.ncbi.nlm.nih.gov/books/NBK1247/. Accessed 30 Aug 2011.

  8. Wong MW, Nordfors C, Mossman D, et al. BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer. Breast Cancer Res Treat. 2011;127:853–9.

    Article  PubMed  CAS  Google Scholar 

  9. Watson P, Vasen HF, Mecklin JP, et al. The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome. Int J Cancer. 2008;123:444–9.

    Article  PubMed  CAS  Google Scholar 

  10. Antoniou AC, Gayther SA, Stratton JF, Ponder BA, Easton DF. Risk models for familial ovarian and breast cancer. Genet Epidemiol. 2000;18:173–90.

    Article  PubMed  CAS  Google Scholar 

  11. Group ABCS. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000;83:1301–8.

    Article  Google Scholar 

  12. Kurian AW. BRCA1 and BRCA2 mutations across race and ethnicity: distribution and clinical implications. Curr Opin Obstet Gynecol. 2010;22:72–8.

    Article  PubMed  Google Scholar 

  13. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336:1401–8.

    Article  PubMed  CAS  Google Scholar 

  14. Pellegrini L, Venkitaraman A. Emerging functions of BRCA2 in DNA recombination. Trends Biochem Sci. 2004;29:310–6.

    Article  PubMed  CAS  Google Scholar 

  15. Shuen AY, Foulkes WD. Inherited mutations in breast cancer genes–risk and response. J Mammary Gland Biol Neoplasia. 2011;16:3–15.

    Article  PubMed  Google Scholar 

  16. Wu J, Lu LY, Yu X. The role of BRCA1 in DNA damage response. Protein Cell. 2010;1:117–23.

    Article  PubMed  Google Scholar 

  17. Knudson Jr AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68:820–3.

    Article  PubMed  Google Scholar 

  18. Abkevich V, Zharkikh A, Deffenbaugh AM, et al. Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. J Med Genet. 2004;41:492–507.

    Article  PubMed  CAS  Google Scholar 

  19. Hirsch B, Shimamura A, Moreau L, et al. Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood. 2004;103:2554–9.

    Article  PubMed  CAS  Google Scholar 

  20. Wagner JE, Tolar J, Levran O, et al. Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia. Blood. 2004;103:3226–9.

    Article  PubMed  CAS  Google Scholar 

  21. Atchley DP, Albarracin CT, Lopez A, et al. Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J Clin Oncol. 2008;26:4282–8.

    Article  PubMed  Google Scholar 

  22. Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81.

    Article  PubMed  Google Scholar 

  23. Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene. 2006;25:5846–53.

    Article  PubMed  CAS  Google Scholar 

  24. National Comprehensive Cancer Network. Practice guidelines in oncology-V.1. 2011. http://www.nccn.org. Accessed 30 Aug 2011.

  25. Nathanson KL, Domchek SM. Therapeutic approaches for women predisposed to breast cancer. Annu Rev Med. 2011;62:295–306.

    Article  PubMed  CAS  Google Scholar 

  26. Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117–30.

    Article  PubMed  CAS  Google Scholar 

  27. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 2008;299:194–201.

    Article  PubMed  CAS  Google Scholar 

  28. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25:1329–33.

    Article  PubMed  Google Scholar 

  29. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994;343:692–5.

    Article  PubMed  CAS  Google Scholar 

  30. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–6.

    Article  PubMed  CAS  Google Scholar 

  31. Risch HA, McLaughlin JR, Cole DE, et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J Natl Cancer Inst. 2006;98:1694–706.

    Article  PubMed  CAS  Google Scholar 

  32. 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;62:676–89.

    Article  PubMed  CAS  Google Scholar 

  33. Whittemore AS, Gong G, Itnyre J. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case–control studies of ovarian cancer. Am J Hum Genet. 1997;60:496–504.

    PubMed  CAS  Google Scholar 

  34. Casey MJ, Synder C, Bewtra C, Narod SA, Watson P, Lynch HT. Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations. Gynecol Oncol. 2005;97:457–67.

    Article  PubMed  Google Scholar 

  35. Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA. 2006;296:185–92.

    Article  PubMed  CAS  Google Scholar 

  36. Medeiros F, Muto MG, Lee Y, et al. The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol. 2006;30:230–6.

    Article  PubMed  Google Scholar 

  37. Consortium TBCL. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst. 1999;91:1310–6.

    Article  Google Scholar 

  38. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–35.

    Article  PubMed  CAS  Google Scholar 

  39. Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27:5887–92.

    Article  PubMed  Google Scholar 

  40. Malone KE, Begg CB, Haile RW, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.

    Article  PubMed  CAS  Google Scholar 

  41. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005;42:711–9.

    Article  PubMed  Google Scholar 

  42. Klein AP, Brune KA, Petersen GM, et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64:2634–8.

    Article  PubMed  CAS  Google Scholar 

  43. Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002;94:1358–65.

    Article  PubMed  CAS  Google Scholar 

  44. Liede A, Karlan BY, Narod SA. Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review of the literature. J Clin Oncol. 2004;22:735–42.

    Article  PubMed  CAS  Google Scholar 

  45. Myriad Genetic Laboratories, Inc. Professional practice guidelines. 2011. http://www.myriadpro.com/guidelines. Accessed 30 Aug 2011.

  46. Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93:1633–7.

    Article  PubMed  CAS  Google Scholar 

  47. Heemskerk-Gerritsen BA, Brekelmans CT, Menke-Pluymers MB, et al. Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic. Ann Surg Oncol. 2007;14:3335–44.

    Article  PubMed  Google Scholar 

  48. Kauff ND, Domchek SM, Friebel TM, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26:1331–7.

    Article  PubMed  Google Scholar 

  49. Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346:1609–15.

    Article  PubMed  Google Scholar 

  50. Rebbeck TR, Friebel T, Wagner T, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23:7804–10.

    Article  PubMed  CAS  Google Scholar 

  51. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–7.

    Article  PubMed  CAS  Google Scholar 

  52. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–22.

    Article  PubMed  Google Scholar 

  53. van Sprundel TC, Schmidt MK, Rookus MA, et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer. 2005;93:287–92.

    Article  PubMed  Google Scholar 

  54. King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001;286:2251–6.

    Article  PubMed  CAS  Google Scholar 

  55. Robson M. Tamoxifen for primary breast cancer prevention in BRCA heterozygotes. Eur J Cancer. 2002;38 Suppl 6:S18–9.

    Article  PubMed  Google Scholar 

  56. Beral V, Doll R, Hermon C, Peto R, Reeves G. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008;371:303–14.

    Article  PubMed  CAS  Google Scholar 

  57. McLaughlin JR, Risch HA, Lubinski J, et al. Reproductive risk factors for ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case–control study. Lancet Oncol. 2007;8:26–34.

    Article  PubMed  CAS  Google Scholar 

  58. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89.

    Article  PubMed  Google Scholar 

  59. Warner E, Plewes DB, Hill KA, et al. Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA. 2004;292:1317–25.

    Article  PubMed  CAS  Google Scholar 

  60. Julian-Reynier C, Mancini J, Mouret-Fourme E, et al. Cancer risk management strategies and perceptions of unaffected women 5 years after predictive genetic testing for BRCA1/2 mutations. Eur J Hum Genet. 2011;19:500–6.

    Article  PubMed  CAS  Google Scholar 

  61. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, et al. International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer. 2008;122:2017–22.

    Article  PubMed  CAS  Google Scholar 

  62. Schwartz MD, Isaacs C, Graves KD, et al. Long-term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance. Cancer. 2012;118(2):510–7.

    Article  PubMed  Google Scholar 

  63. National Cancer Institute. Breast cancer prevention (PDQ). 2011. http://www.cancer.gov/cancertopics/pdq/prevention/breast/HealthProfessional/page2. Accessed 30 Aug 2011.

  64. Bissonauth V, Shatenstein B, Fafard E, et al. Weight history, smoking, physical activity and breast cancer risk among French-Canadian women non-carriers of more frequent BRCA1/2 mutations. J Cancer Epidemiol. 2009;2009:748367.

    PubMed  Google Scholar 

  65. Lecarpentier J, Nogues C, Mouret-Fourme E, et al. Variation in breast cancer risk with mutation position, smoking, alcohol, and chest X-ray history, in the French National BRCA1/2 carrier cohort (GENEPSO). Breast Cancer Res Treat. 2011;130(3):927–38.

    Article  PubMed  CAS  Google Scholar 

  66. Pijpe A, Manders P, Brohet RM, et al. Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat. 2010;120:235–44.

    Article  PubMed  Google Scholar 

  67. Schwartz MD, Lerman C, Brogan B, et al. Impact of BRCA1/BRCA2 counseling and testing on newly diagnosed breast cancer patients. J Clin Oncol. 2004;22:1823–9.

    Article  PubMed  Google Scholar 

  68. Schwartz MD, Lerman C, Brogan B, et al. Utilization of BRCA1/BRCA2 mutation testing in newly diagnosed breast cancer patients. Cancer Epidemiol Biomarkers Prev. 2005;14:1003–7.

    Article  PubMed  CAS  Google Scholar 

  69. Tai YC, Domchek S, Parmigiani G, Chen S. Breast cancer risk among male BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2007;99:1811–4.

    Article  PubMed  CAS  Google Scholar 

  70. NCCN recommendations for BRCA1/2 mutation carriers. 2011. http://www.nccn.org/professionals/physician_gls/PDF/genetics_screening.pdf.

  71. Canto MI. Screening and surveillance approaches in familial pancreatic cancer. Gastrointest Endosc Clin N Am. 2008;18:535–53; x.

    Google Scholar 

  72. Byrski T, Gronwald J, Huzarski T, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28:375–9.

    Article  PubMed  CAS  Google Scholar 

  73. Byrski T, Huzarski T, Dent R, et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2009;115:359–63.

    Article  PubMed  CAS  Google Scholar 

  74. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.

    Article  PubMed  CAS  Google Scholar 

  75. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.

    Article  PubMed  CAS  Google Scholar 

  76. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–34.

    Article  PubMed  CAS  Google Scholar 

  77. Myriad Genetic Laboratories I. In; 2011.

    Google Scholar 

  78. Saiki RK, Gelfand DH, Stoffel S, et al. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988;239:487–91.

    Article  PubMed  CAS  Google Scholar 

  79. Wilson RK, Chen C, Avdalovic N, Burns J, Hood L. Development of an automated procedure for fluorescent DNA sequencing. Genomics. 1990;6:626–34.

    Article  PubMed  CAS  Google Scholar 

  80. Brzovic PS, Meza J, King MC, Klevit RE. The cancer-predisposing mutation C61G disrupts homodimer formation in the NH2-terminal BRCA1 RING finger domain. J Biol Chem. 1998;273:7795–9.

    Article  PubMed  CAS  Google Scholar 

  81. Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet. 1995;11:198–200.

    Article  PubMed  CAS  Google Scholar 

  82. MRC-Holland. 2011. http://www.mlpa.com/WebForms/WebFormMain.aspx. Accessed 2 Nov 2011.

  83. Kauff ND, Mitra N, Robson ME, et al. Risk of ovarian cancer in BRCA1 and BRCA2 mutation-negative hereditary breast cancer families. J Natl Cancer Inst. 2005;97:1382–4.

    Article  PubMed  CAS  Google Scholar 

  84. Richards CS, Bale S, Bellissimo DB, et al. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med. 2008;10:294–300.

    Article  PubMed  CAS  Google Scholar 

  85. Plon SE, Eccles DM, Easton D, et al. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat. 2008;29:1282–91.

    Article  PubMed  CAS  Google Scholar 

  86. Mazoyer S, Dunning AM, Serova O, et al. A polymorphic stop codon in BRCA2. Nat Genet. 1996;14:253–4.

    Article  PubMed  CAS  Google Scholar 

  87. Chapman MS, Verma IM. Transcriptional activation by BRCA1. Nature. 1996;382:678–9.

    Article  PubMed  CAS  Google Scholar 

  88. Haile DT, Parvin JD. Activation of transcription in vitro by the BRCA1 carboxyl-terminal domain. J Biol Chem. 1999;274:2113–7.

    Article  PubMed  CAS  Google Scholar 

  89. Kais Z, Chiba N, Ishioka C, Parvin JD. Functional differences among BRCA1 missense mutations in the control of centrosome duplication. Oncogene. 2012;31(6):799–804.

    Article  PubMed  CAS  Google Scholar 

  90. MacLachlan TK, Somasundaram K, Sgagias M, et al. BRCA1 effects on the cell cycle and the DNA damage response are linked to altered gene expression. J Biol Chem. 2000;275:2777–85.

    Article  PubMed  CAS  Google Scholar 

  91. Monteiro AN, August A, Hanafusa H. Evidence for a transcriptional activation function of BRCA1 C-terminal region. Proc Natl Acad Sci USA. 1996;93:13595–9.

    Article  PubMed  CAS  Google Scholar 

  92. Moynahan ME, Chiu JW, Koller BH, Jasin M. Brca1 controls homology-directed DNA repair. Mol Cell. 1999;4:511–8.

    Article  PubMed  CAS  Google Scholar 

  93. Parvin J, Chiba N, Ransburgh D. Identifying the effects of BRCA1 mutations on homologous recombination using cells that express endogenous wild-type BRCA1. J Vis Exp. 2011;48. doi: 10.3791/2468.

  94. Lee MS, Green R, Marsillac SM, et al. Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. Cancer Res. 2010;70:4880–90.

    Article  PubMed  CAS  Google Scholar 

  95. Farrugia DJ, Agarwal MK, Pankratz VS, et al. Functional assays for classification of BRCA2 variants of uncertain significance. Cancer Res. 2008;68:3523–31.

    Article  PubMed  CAS  Google Scholar 

  96. Adzhubei IA, Schmidt S, Peshkin L, et al. A method and server for predicting damaging missense mutations. Nat Methods. 2010;7:248–9.

    Article  PubMed  CAS  Google Scholar 

  97. Ng PC, Henikoff S. Predicting deleterious amino acid substitutions. Genome Res. 2001;11:863–74.

    Article  PubMed  CAS  Google Scholar 

  98. Sunyaev S, Ramensky V, Koch I, Lathe 3rd W, Kondrashov AS, Bork P. Prediction of deleterious human alleles. Hum Mol Genet. 2001;10:591–7.

    Article  PubMed  CAS  Google Scholar 

  99. Gowen LC, Johnson BL, Latour AM, Sulik KK, Koller BH. Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities. Nat Genet. 1996;12:191–4.

    Article  PubMed  CAS  Google Scholar 

  100. Hakem R, de la Pompa JL, Sirard C, et al. The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell. 1996;85:1009–23.

    Article  PubMed  CAS  Google Scholar 

  101. Hohenstein P, Kielman MF, Breukel C, et al. A targeted mouse Brca1 mutation removing the last BRCT repeat results in apoptosis and embryonic lethality at the headfold stage. Oncogene. 2001;20:2544–50.

    Article  PubMed  CAS  Google Scholar 

  102. Liu CY, Flesken-Nikitin A, Li S, Zeng Y, Lee WH. Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. Genes Dev. 1996;10:1835–43.

    Article  PubMed  CAS  Google Scholar 

  103. Ludwig T, Chapman DL, Papaioannou VE, Efstratiadis A. Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev. 1997;11:1226–41.

    Article  PubMed  CAS  Google Scholar 

  104. Frank TS, Deffenbaugh AM, Reid JE, et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol. 2002;20:1480–90.

    Article  PubMed  CAS  Google Scholar 

  105. Tavtigian SV, Byrnes GB, Goldgar DE, Thomas A. Classification of rare missense substitutions, using risk surfaces, with genetic- and molecular-epidemiology applications. Hum Mutat. 2008;29:1342–54.

    Article  PubMed  CAS  Google Scholar 

  106. Tavtigian SV, Samollow PB, de Silva D, Thomas A. An analysis of unclassified missense substitutions in human BRCA1. Fam Cancer. 2006;5:77–88.

    Article  PubMed  CAS  Google Scholar 

  107. Easton DF, Deffenbaugh AM, Pruss D, et al. A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet. 2007;81:873–83.

    Article  PubMed  CAS  Google Scholar 

  108. Goldgar DE, Easton DF, Byrnes GB, Spurdle AB, Iversen ES, Greenblatt MS. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model. Hum Mutat. 2008;29:1265–72.

    Article  PubMed  Google Scholar 

  109. Ambry Genetics. XLMR testing options. 2011. http://www.ambrygen.com/X-Linked-Intellectual-Disabilities.html. Accessed 30 Aug 2011.

  110. Emory Genetics Laboratory. Congenital muscular dystrophy comprehensive next generation sequencing panel. 2011. http://genetics.emory.edu/egl/tests/?testid=440. Accessed 30 Aug 2011.

  111. Walsh T, Lee MK, Casadei S, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci USA. 2010;107:12629–33.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA

    Karla R. Bowles Ph.D. & Eric Rosenthal Ph.D., Sc.M

Authors
  1. Karla R. Bowles Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Rosenthal Ph.D., Sc.M
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Karla R. Bowles Ph.D. .

Editor information

Editors and Affiliations

  1. Medicine and Pathology Molecular Genetics Laboratory, Mayo Clinic College of Medicine Department of Laboratory, Rochester, Minnesota, USA

    W. Edward Highsmith, Jr.

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Bowles, K.R., Rosenthal, E. (2014). BRCA1 and BRCA2 Testing in Inherited Breast Cancer. In: Highsmith, Jr., W. (eds) Molecular Diagnostics. Molecular and Translational Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8127-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8127-0_10

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4614-8126-3

  • Online ISBN: 978-1-4614-8127-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation