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A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes

Breast Cancer volume 22, pages 557–561 (2015)Cite this article

Abstract

We report an extremely rare case of familial breast cancer with deleterious germline mutations in both BRCA1 and BRCA2 genes, of which, to date, no such case has been reported among Japanese breast/ovarian cancer patients. Genetic testing of the family members indicated that the same double heterozygosity for BRCA1 and BRCA2 genes was transmitted to the paternal cousin, and the same BRCA2 mutation to the younger sister with bilateral breast cancer, younger brother with stomach cancer, and proband’s son and daughter without cancer. Immunohistochemical analysis of BRCA protein expression was performed using breast cancer tissues from the proband with double heterozygosity for BRCA1 and BRCA2 genes and from her sibling without BRCA1 mutation but with BRCA2 mutation. There was no staining of either BRCA in the proband and no staining of BRCA2 in the sibling.

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References

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

    PubMed  CAS  Article  Google Scholar 

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

    PubMed  CAS  Article  Google Scholar 

  3. Nomizu T, Tsuchiya A, Kanno M, Katagata N, Watanabe F, Yamaki Y, et al. Clinicopathological features of hereditary breast cancer. Breast Cancer. 1997;4:239–42.

    PubMed  Article  Google Scholar 

  4. Nomizu T, Abe R, Tsuchiya A, Utsunomiya J, Watanabe F, Yamaki Y. A clinical study of familial cancer in Japan. In: Weber W, editor. Familial cancer control. European School of Oncology Monographs. Berlin: Springer; 1992. p. 105–11.

    Chapter  Google Scholar 

  5. Frank TS, Deffenbaugh AM, Reid JE, Hulick M, Ward BE, Lingenfelter B, 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.

    PubMed  CAS  Article  Google Scholar 

  6. Leegte B, van der Hout AH, Deffenbaugh AM, Bakker MK, Mulder IM, ten Berge A, et al. Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline mutations. J Med Genet. 2005;42(3):e20.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  7. Ramus SJ, Friedman LS, Gayther SA, Ponder BA, Bobrow L, van der Looji M, et al. A breast/ovarian cancer patient with germline mutations in both BRCA1 and BRCA2. Nat Genet. 1997;15:14–5.

    PubMed  CAS  Article  Google Scholar 

  8. Liede A, Rehal P, Vesprini D, Jack E, Abrahamson J, Narod S. A breast cancer patient of Scottish descent with germ-line mutations in BRCA1 and BRCA2. Am J Hum Genet. 1998;62:1543–4.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  9. Friedman E, Bruchim RBS, Kruglikova A, Risel S, Levy-Lahad E, Halle D, et al. Double heterozygotes for the Ashkenazi founder mutation in BRCA1 and BRCA2 genes. Am J Hun Genet. 1998;63:1224–7.

    CAS  Article  Google Scholar 

  10. Loader S, Rowley PT. Deleterious mutations of both BRCA1 and BRCA2 in three siblings. Genet Test. 1998;2:75–7.

    PubMed  CAS  Article  Google Scholar 

  11. Randall TC, Bell KA, Rebane BA, Rubin SC, Boyd J. Germline mutations of the BRCA1 and BRCA2 genes in a breast and ovarian cancer patient. Gynecol Oncol. 1998;70:432–4.

    PubMed  CAS  Article  Google Scholar 

  12. Tesoriero A, Andersen C, Southey M, Somers G, McKay M, Armes J, et al. De novo BRCA1 mutation in a patient with breast cancer and an inherited BRCA2 mutation. Am J Hum Genet. 1999;65:567–9.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  13. Moslehi R, Chu W, Karlan B, Fishman D, Risch H, Fields A, et al. BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Am J Hum Genet. 2000;66:1259–72.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  14. Bell DW, Erban J, Sgroi DC, Haber DA. Selective loss of heterozygosity in multiple breast cancers from a carrier of mutations in both BRCA1 and BRCA2. Cancer Res. 2002;62:2741–3.

    PubMed  CAS  Google Scholar 

  15. Caldes T, de la Hoya M, Tosar A, Sulleiro S, Godino J, Ibanez D, et al. A breast cancer family from Spain with germline mutations in both the BRCA1 and BRCA2 genes. J Med Genet. 2002;39:e44.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  16. Claus EB, Petruzella S, Matloff E, Carter D. Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ. JAMA. 2005;293:964–9.

    PubMed  CAS  Article  Google Scholar 

  17. Smith M, Fawcett S, Sigalas E, Bell R, Devery S, Andrieska N, et al. Familial breast cancer: double heterozygosity for BRCA1 and BRCA2 mutations with differing phenotypes. Fam Cancer. 2008;7:119–24.

    PubMed  CAS  Article  Google Scholar 

  18. Steffensen AY, Jønson L, Ejlertsen B, Gerdes AM, Nielsen FC, Hansen TVO. Identification of a Danish breast/ovarian cancer family double heterozygote for BRCA1 and BRCA2 mutations. Fam Cancer. 2010;9:283–7.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  19. Zuradelli M, Peissel B, Manoukian S, Zaffaroni D, Barile M, Pensotti V, et al. Four new cases of double heterozygosity for BRCA1 and BRCA2 gene mutations: clinical, pathological, and family characteristics. Breast Cancer Res Treat. 2010;124:251–8.

    PubMed  CAS  Article  Google Scholar 

  20. Pilato B, De Summa S, Danza K, Lambo R, Paradiso A, Tommasi S. Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report. Breast Cancer Res Treat. 2010;124:875–8.

    PubMed  Article  Google Scholar 

  21. Lavie O, Narod S, Lejbkowicz F, Dishon S, Goldberg Y, Gemer O, et al. Double heterozygosity in the BRCA1 and BRCA2 genes in the Jewish population. Ann Oncol. 2011;22:964–6.

    PubMed  CAS  Article  PubMed Central  Google Scholar 

  22. Heidemann S, Fischer C, Engel C, Fischer B, Harder L, Schlegelberger B, et al. Double heterozygosity for mutation in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management. Breast Cancer Res Treat. 2012;134:1229–39.

    PubMed  CAS  Article  Google Scholar 

  23. Choi DH, Lee MH, Haffty BG. Double heterozygotes for non-Caucasian families with mutations in BRCA-1 and BRCA-2 genes. Breast J. 2006;12:216–20.

    PubMed  CAS  Article  Google Scholar 

  24. Noh JM, Choi DH, Nam SJ, Lee JE, Kim JW, Kim SW, et al. Characteristics of double heterozygosity for BRCA1 and BRCA2 germline mutations in Korean breast cancer patients. Breast Cancer Res Treat. 2012;131:217–22.

    PubMed  CAS  Article  Google Scholar 

  25. Sugano K, Nakamaura S, Ando J, Takayama S, Kamata H, Sekiguchi I, et al. Cross-sectional analysis of germline BRCA1 and BRCA2 mutations in Japanese patients suspected to have hereditary breast/ovarian cancer. Cancer Sci. 2008;99:1967–76.

    PubMed  CAS  Article  Google Scholar 

  26. Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. Med Gen Med. 2005;7(2):60.

    Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Affiliations

  1. Department of Surgery and Breast Surgery, Hoshi General Hospital, 2-1-16 Omachi, Koriyama, 963-8501, Japan

    Tadashi Nomizu, Masami Matsuzaki, Naoto Katagata, Yusuke Kobayashi, Takeshi Sakuma, Tomoyuki Monma, Motonobu Saito & Fumiaki Watanabe

  2. Clinic of Familial Tumor, Hoshi General Hospital, Koriyama, Japan

    Tadashi Nomizu

  3. Department of Pathology, Hoshi General Hospital, Koriyama, Japan

    Shinichi Midorikawa & Yoshiko Yamaguchi

Authors
  1. Tadashi Nomizu
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  2. Masami Matsuzaki
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  3. Naoto Katagata
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  4. Yusuke Kobayashi
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  5. Takeshi Sakuma
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  6. Tomoyuki Monma
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  7. Motonobu Saito
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  8. Fumiaki Watanabe
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  9. Shinichi Midorikawa
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  10. Yoshiko Yamaguchi
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Correspondence to Tadashi Nomizu.

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Nomizu, T., Matsuzaki, M., Katagata, N. et al. A case of familial breast cancer with double heterozygosity for BRCA1 and BRCA2 genes. Breast Cancer 22, 557–561 (2015). https://doi.org/10.1007/s12282-012-0432-4

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  • DOI: https://doi.org/10.1007/s12282-012-0432-4

Keywords

  • Familial breast cancer
  • Hereditary breast cancer
  • Hereditary breast/ovarian cancer
  • BRCA gene
  • Immunohistochemical staining