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Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report

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Abstract

Hereditary breast cancer syndrome was firstly associated with BRCA1 and BRCA2 genes the mutations of which confer high risk to develop breast and/or ovarian cancer. Double heterozygosity is a rare condition in which both BRCA1 and BRCA2 mutations are present in a family at the same time. In the current study, a family with double heterozygosity has been reported. Furthermore, for the first time a molecular analysis in both proband lineages, maternal and paternal, has been reported to understand the provenience of both germinal mutations.The case regards a woman who developed breast and ovarian cancer with liver metastasis which presented two mutations, each in the two genes, transmitted from her mother and her father, respectively. In this family all available members have been investigated. The concomitant presence of these peculiar mutations was never reported before suggesting a link with Caucasian population from Southern Italy.

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References

  1. Tommasi S, Pilato B, Pinto R, Monaco A, Bruno M, Campana M, Digennaro M, Schittulli F, Lacalamita R, Paradiso A (2008) Molecular and in silico analysis of brca1 and brca2 variants. Mutat Res 644(1–2):64–70. doi:S0027-5107(08)00135-8

    CAS  PubMed  Google Scholar 

  2. Diez O, Gutierrez-Enriquez S, Masas M, Tenes A, Yague C, Arcusa A, Llort G (2010) Identification of a new complex deleterious mutation in exon 18 of the brca2 gene in a hereditary male/female breast cancer family. Breast Cancer Res Treat. doi:10.1007/s10549-010-0830-2

  3. Pilato B, Martinucci M, Danza K, Pinto R, Petriella D, Lacalamita R, Bruno M, Lambo R, D’Amico C, Paradiso A, Tommasi S (2010) Mutations and polymorphic brca variants transmission in breast cancer familial members. Breast Cancer Res Treat. doi:10.1007/s10549-010-0861-8

  4. Sluiter MD, van Rensburg EJ (2010) Large genomic rearrangements of the brca1 and brca2 genes: Review of the literature and report of a novel brca1 mutation. Breast Cancer Res Treat. doi:10.1007/s10549-010-0817-z

  5. Zuradelli M, Peissel B, Manoukian S, Zaffaroni D, Barile M, Pensotti V, Cavallari U, Masci G, Mariette F, Benski AC, Santoro A, Radice P (2010) Four new cases of double heterozygosity for brca1 and brca2 gene mutations: Clinical, pathological, and family characteristics. Breast Cancer Res Treat. doi:10.1007/s10549-010-0853-8

  6. Cortesi L, Turchetti D, Bertoni C, Zanocco-Marani T, Vinceti M, Silvestri C, Federico M, Silingardi V, Ferrari S (2003) Italian family with two independent mutations: 3358t/a in brca1 and 8756dela in brca2 genes. Eur J Hum Genet 11(3):210–214. doi:10.1038/sj.ejhg.52009485200948

    Article  CAS  PubMed  Google Scholar 

  7. Musolino A, Naldi N, Michiara M, Bella MA, Zanelli P, Bortesi B, Capelletti M, Savi M, Neri TM, Ardizzoni A (2005) A breast cancer patient from Italy with germline mutations in both the brca1 and brca2 genes. Breast Cancer Res Treat 91(2):203–205. doi:10.1007/s10549-004-7704-4

    Article  PubMed  Google Scholar 

  8. Tommasi S, Crapolicchio A, Lacalamita R, Bruno M, Monaco A, Petroni S, Schittulli F, Longo S, Digennaro M, Calistri D, Mangia A, Paradiso A (2005) Brca1 mutations and polymorphisms in a hospital-based consecutive series of breast cancer patients from apulia, Italy. Mutat Res 578(1–2):395–405. doi:S0027-5107(05)00250-2

    CAS  PubMed  Google Scholar 

  9. Berry DA, Iversen ES Jr, Gudbjartsson DF, Hiller EH, Garber JE, Peshkin BN, Lerman C, Watson P, Lynch HT, Hilsenbeck SG, Rubinstein WS, Hughes KS, Parmigiani G (2002) Brcapro validation, sensitivity of genetic testing of brca1/brca2, and prevalence of other breast cancer susceptibility genes. J Clin Oncol 20(11):2701–2712

    Article  CAS  PubMed  Google Scholar 

  10. Leegte B, van der Hout AH, Deffenbaugh AM, Bakker MK, Mulder IM, ten Berge A, Leenders EP, Wesseling J, de Hullu J, Hoogerbrugge N, Ligtenberg MJ, Ardern-Jones A, Bancroft E, Salmon A, Barwell J, Eeles R, Oosterwijk JC (2005) Phenotypic expression of double heterozygosity for brca1 and brca2 germline mutations. J Med Genet 42(3):e20. doi:42/3/e20

    Article  CAS  PubMed  Google Scholar 

  11. Abeliovich D, Kaduri L, Lerer I, Weinberg N, Amir G, Sagi M, Zlotogora J, Heching N, Peretz T (1997) The founder mutations 185delag and 5382insc in brca1 and 6174delt in brca2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 60(3):505–514

    CAS  PubMed  Google Scholar 

  12. Rennert G, Dishon S, Rennert HS, Fares F (2005) Differences in the characteristics of families with brca1 and brca2 mutations in Israel. Eur J Cancer Prev 14(4):357–361. doi:00008469-200508000-00008

    Article  CAS  PubMed  Google Scholar 

  13. Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, Offit K (2002) Ovarian cancer risk in Ashkenazi Jewish carriers of brca1 and brca2 mutations. Clin Cancer Res 8(12):3776–3781

    CAS  PubMed  Google Scholar 

  14. Kataki A, Gomatos I, Pararas N, Armakolas A, Panousopoulos D, Karantzikos G, Voros D, Zografos G, Markopoulos C, Leandros E, Konstadoulakis M (2005) Identification of germline brca1 and brca2 genetic alterations in Greek breast cancer moderate-risk and low-risk individuals—correlation with clinicopathological data. Clin Genet 67(4):322–329. doi:CGE400

    Article  CAS  PubMed  Google Scholar 

  15. De Benedetti VM, Radice P, Pasini B, Stagi L, Pensotti V, Mondini P, Manoukian S, Conti A, Spatti G, Rilke F, Pierotti MA (1998) Characterization of ten novel and 13 recurring brca1 and brca2 germline mutations in Italian breast and/or ovarian carcinoma patients. Mutations in brief no. 178. Online. Hum Mutat 12(3):215

    Google Scholar 

  16. Armakolas A, Ladopoulou A, Konstantopoulou I, Pararas B, Gomatos IP, Kataki A, Konstadoulakis MM, Stathopoulos GP, Markopoulos C, Leandros E, Gogas I, Yannoukakos D, Androulakis G (2002) Brca2 gene mutations in Greek patients with familial breast cancer. Hum Mutat 19(1):81–82. doi:10.1002/humu.9003

    Article  PubMed  Google Scholar 

  17. Moslehi R, Russo D, Phelan C, Jack E, Antman K, Narod S (2000) An unaffected individual from a breast/ovarian cancer family with germline mutations in both brca1 and brca2. Clin Genet 57(1):70–73

    Article  CAS  PubMed  Google Scholar 

  18. Bell DW, Erban J, Sgroi DC, Haber DA (2002) Selective loss of heterozygosity in multiple breast cancers from a carrier of mutations in both brca1 and brca2. Cancer Res 62(10):2741–2743

    CAS  PubMed  Google Scholar 

  19. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA (1997) The risk of cancer associated with specific mutations of brca1 and brca2 among Ashkenazi Jews. N Engl J Med 336(20):1401–1408. doi:10.1056/NEJM199705153362001

    Article  CAS  PubMed  Google Scholar 

  20. Warner E, Foulkes W, Goodwin P, Meschino W, Blondal J, Paterson C, Ozcelik H, Goss P, Allingham-Hawkins D, Hamel N, Di Prospero L, Contiga V, Serruya C, Klein M, Moslehi R, Honeyford J, Liede A, Glendon G, Brunet JS, Narod S (1999) Prevalence and penetrance of brca1 and brca2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91(14):1241–1247

    Article  CAS  PubMed  Google Scholar 

  21. Satagopan JM, Offit K, Foulkes W, Robson ME, Wacholder S, Eng CM, Karp SE, Begg CB (2001) The lifetime risks of breast cancer in Ashkenazi Jewish carriers of brca1 and brca2 mutations. Cancer Epidemiol Biomarkers Prev 10(5):467–473

    CAS  PubMed  Google Scholar 

  22. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for brca1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94(18):1365–1372

    CAS  PubMed  Google Scholar 

  23. King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in brca1 and brca2. Science 302(5645):643–646. doi:10.1126/science.1088759302/5645/643

    Article  CAS  PubMed  Google Scholar 

  24. Claus EB, Petruzella S, Matloff E, Carter D (2005) Prevalence of brca1 and brca2 mutations in women diagnosed with ductal carcinoma in situ. JAMA 293(8):964–969. doi:293/8/964

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was partially supported by Regione Puglia (DIEF 2007).

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Authors and Affiliations

  1. Clinical Experimental Oncology Laboratory, National Cancer Centre, “Giovanni Paolo II”- v. Hahnemann 10, 70126, Bari, Italy

    Brunella Pilato, Simona De Summa, Katia Danza, Rossana Lambo, Angelo Paradiso & Stefania Tommasi

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  1. Brunella Pilato
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  2. Simona De Summa
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  3. Katia Danza
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  4. Rossana Lambo
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  5. Angelo Paradiso
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  6. Stefania Tommasi
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Correspondence to Stefania Tommasi.

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Pilato, B., De Summa, S., Danza, K. et al. Maternal and paternal lineage double heterozygosity alteration in familial breast cancer: a first case report. Breast Cancer Res Treat 124, 875–878 (2010). https://doi.org/10.1007/s10549-010-1125-3

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  • DOI: https://doi.org/10.1007/s10549-010-1125-3

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