Top

Published in:

Open Access 01-12-2009 | Case report

Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing

Authors: Anna P Sokolenko, Dmitry A Voskresenskiy, Aglaya G Iyevleva, Elena M Bit-Sava, Nadezhda I Gutkina, Maxim S Anisimenko, Nathalia Yu Sherina, Nathalia V Mitiushkina, Yulia M Ulibina, Olga S Yatsuk, Olga A Zaitseva, Evgeny N Suspitsin, Alexandr V Togo, Valery A Pospelov, Sergey P Kovalenko, Vladimir F Semiglazov, Evgeny N Imyanitov

Published in: Hereditary Cancer in Clinical Practice | Issue 1/2009

Abstract

Although the probability of both parents being affected by BRCA1 mutations is not negligible, such families have not been systematically described in the literature. Here we present a large breast-ovarian cancer family, where 3 sisters and 1 half-sister inherited maternal BRCA1 5382insC mutation while the remaining 2 sisters carried paternal BRCA1 1629delC allele. No BRCA1 homozygous mutations has been detected, that is consistent with the data on lethality of BRCA1 knockout mice. This report exemplifies that the identification of a single cancer-predisposing mutation within the index patient may not be sufficient in some circumstances. Ideally, all family members affected by breast or ovarian tumor disease have to be subjected to the DNA testing, and failure to detect the mutation in any of them calls for the search of the second cancer-associated allele.

Available only for authorised users

Nathanson KL, Wooster R, Weber BL: Breast cancer genetics: what we know and what we need. Nat Med 2001, 7: 552–556. 10.1038/87876CrossRefPubMed

Satagopan JM, Offit K, Foulkes W, Robson ME, Wacholder S, Eng CM, Karp SE, Begg CB: The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev 2001, 10: 467–473.PubMed

Menkiszak J, Gronwald J, Górski B, Jakubowska A, Huzarski T, Byrski T, Foszczyńska-Kłoda M, Haus O, Janiszewska H, Perkowska M, Brozek I, Grzybowska E, Zientek H, Góźdź S, Kozak-Klonowska B, Urbański K, Miturski R, Kowalczyk J, Pluzańska A, Niepsuj S, Koc J, Szwiec M, Drosik K, Mackiewicz A, Lamperska K, Strózyk E, Godlewski D, Stawicka M, Waśko B, Bebenek M, Rozmiarek A, Rzepka-Górska I, Narod SA, Lubiński J: Hereditary ovarian cancer in Poland. Int J Cancer 2003, 106: 942–945. 10.1002/ijc.11338CrossRefPubMed

Whittemore AS, Gong G, John EM, McGuire V, Li FP, Ostrow KL, Dicioccio R, Felberg A, West DW: Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites. Cancer Epidemiol Biomarkers Prev 2004, 13: 2078–2083.PubMed

Narod SA, Foulkes WD: BRCA1 and BRCA2: 1994 and beyond. Nat Rev Cancer 2004, 4: 665–676. 10.1038/nrc1431CrossRefPubMed

Górski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbański K, Mituś J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Tołoczko-Grabarek A, Medrek K, Masojæ B, Mierzejewski M, Kowalska E, Narod SA, Lubiński J: Breast cancer predisposing alleles in Poland. Breast Cancer Res Treat 2005, 92: 19–24. 10.1007/s10549-005-1409-1CrossRefPubMed

Robson M, Offit K: Clinical practice. Management of an inherited predisposition to breast cancer. New Engl J Med 2007, 357: 154–162. 10.1056/NEJMcp071286CrossRefPubMed

Sokolenko AP, Rozanov ME, Mitiushkina NV, Sherina NY, Iyevleva AG, Chekmariova EV, Buslov KG, Shilov ES, Togo AV, Bit-Sava EM, Voskresenskiy DA, Chagunava OL, Devilee P, Cornelisse C, Semiglazov VF, Imyanitov EN: Founder mutations in early-onset, familial and bilateral breast cancer patients from Russia. Fam Cancer 2007, 6: 281–286. 10.1007/s10689-007-9120-5CrossRefPubMed

Boyd M, Harris F, McFarlane R, Davidson HR, Black DM: A human BRCA1 gene knockout. Nature 1995, 375: 541–542. 10.1038/375541b0CrossRefPubMed

10.

Kuschel B, Gayther SA, Easton DF, Ponder BA, Pharoah PD: Apparent human BRCA1 knockout caused by mispriming during polymerase chain reaction: implications for genetic testing. Genes Chromosomes Cancer 2001, 31: 96–98. 10.1002/gcc.1122CrossRefPubMed

11.

Stoppa-Lyonnet D, Fricker JP, Essioux L, Pages S, Limacher JM, Sobol H, Laurent-Puig P, Thomas G: Segregation of two BRCA1 mutations in a single family. Am J Hum Genet 1996, 59: 479–481.PubMedPubMedCentral

12.

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: 191–194. 10.1038/ng0296-191CrossRefPubMed

13.

Hakem R, de la Pompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, Firpo E, Hui CC, Roberts J, Rossant J, Mak TW: The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. Cell 1996, 85: 1009–1023. 10.1016/S0092-8674(00)81302-1CrossRefPubMed

14.

Chandler J, Hohenstein P, Swing DA, Tessarollo L, Sharan SK: Human BRCA1 gene rescues the embryonic lethality of Brca1 mutant mice. Genesis 2001, 29: 72–77. 10.1002/1526-968X(200102)29:2<72::AID-GENE1007>3.0.CO;2-BCrossRefPubMed

15.

Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C, Persky N, Grompe M, Joenje H, Pals G, Ikeda H, Fox EA, D'Andrea AD: Biallelic inactivation of BRCA2 in Fanconi anemia. Science 2002, 297: 606–609. 10.1126/science.1073834CrossRefPubMed

16.

Leegte B, 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: Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline mutations. J Med Genet 2005, 42: e20. 10.1136/jmg.2004.027243CrossRefPubMedPubMedCentral

Title: Large family with both parents affected by distinct BRCA1 mutations: implications for genetic testing
Authors: Anna P Sokolenko
Dmitry A Voskresenskiy
Aglaya G Iyevleva
Elena M Bit-Sava
Nadezhda I Gutkina
Maxim S Anisimenko
Nathalia Yu Sherina
Nathalia V Mitiushkina
Yulia M Ulibina
Olga S Yatsuk
Olga A Zaitseva
Evgeny N Suspitsin
Alexandr V Togo
Valery A Pospelov
Sergey P Kovalenko
Vladimir F Semiglazov
Evgeny N Imyanitov
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Hereditary Cancer in Clinical Practice / Issue 1/2009
Electronic ISSN: 1897-4287
DOI: https://doi.org/10.1186/1897-4287-7-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2009

High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype

Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management

Standard psychological consultations and follow up for women at increased risk of hereditary breast cancer considering prophylactic mastectomy

Factors associated with testicular self-examination among unaffected men from multiple-case testicular cancer families

Risk perception after genetic counseling in patients with increased risk of cancer

Keynote webinar | Spotlight on antibody–drug conjugates in cancer