Abstract
Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27–53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.
This is a preview of subscription content, log in via an institution to check access.
References
Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781
Sanchez MJ, Payer T, De AR, Larranaga N, Capocaccia R, Martinez C (2010) Cancer incidence and mortality in Spain: estimates and projections for the period 1981–2012. Ann Oncol 21(Suppl 3):iii30–iii36
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71
Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792
Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, nton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjakoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) 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 72:1117–1130
BIC (2013). http://research.nhgri.nih.gov/bic/. Accessed 17 July 2013
Database UniSTS (NCBI) (2013). http://www.ncbi.nlm.nih.gov/unists/. Accessed 25 Sept 2013
Sagi M, Eilat A, Ben AL, Goldberg Y, Bercovich D, Hamburger T, Peretz T, Lerer I (2011) Two BRCA1/2 founder mutations in Jews of Sephardic origin. Fam Cancer 10:59–63
The Human Gene Mutation Database (2013). http://www.hgmd.cf.ac.uk/ac/index.php. Accessed 17 July 2013
Universal Mutation Database (UMD) (2013). http://www.umd.be/. Accessed 17 July 2013
Leiden Open Variation Database (LOVD) (2013). http://www.lovd.nl/3.0/home. Accessed 17 July 2013
Huen MS, Sy SM, Chen J (2010) BRCA1 and its toolbox for the maintenance of genome integrity. Nat Rev Mol Cell Biol 11:138–148
Moynahan ME, Jasin M (2010) Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 11:196–207
Zhang F, Fan Q, Ren K, Andreassen PR (2009) PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2. Mol Cancer Res 7:1110–1118
Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B, Yu X (2009) PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol 19:524–529
Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D (2012) Structure-function of the tumor suppressor BRCA1. Comput Struct Biotechnol J 1(1). pii: e201204005
Easton DF, Bishop DT, Ford D, Crockford GP (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The breast cancer linkage consortium. Am J Hum Genet 52:678–701
Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, Cannon-Albright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder B, Stoppa-Lyonnet D, Easton D, King MC, Goldgar DE (1996) Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet 58:271–280
Acknowledgments
We thank the patients, their families and physicians of the Genetic Counselling of the University Hospital Virgen de la Arrixaca (Murcia, Spain) who collaborated in this study. We thank Ángeles Aliaga Baño and Teresa Manzano Baiazitova for excellent technical assistance. We are also gratefully to our dedicated nurse Encarna Cuevas Tortosa for providing samples and for assistance in configuring the pedigree.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gabaldó Barrios, X., Sarabia Meseguer, M.D., Alonso Romero, J.L. et al. Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry. Familial Cancer 13, 431–435 (2014). https://doi.org/10.1007/s10689-014-9708-5
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10689-014-9708-5