부산대학교 도서관

Byline: Laura Papi (1), Anna Laura Putignano (1), Caterina Congregati (1), Ines Zanna (2), Francesco Sera (2), Doralba Morrone (3), Mario Falchetti (4), Marco Rosselli Del Turco (5), Laura Ottini (4), Domenico Palli (2), Maurizio Genuardi (1,6) Keywords: Hereditary breast/ovarian cancer; Male breast cancer; BRCA1; BRCA2; Founder mutation Abstract: Background Germline mutations in the BRCA1 and BRCA2 tumour-suppressor genes predispose to early-onset breast and ovarian cancer. Although both genes display a highly heterogeneous mutation spectrum, a number of alterations recur in some populations. Only a limited number of founder mutations have been identified in the Italian population so far. Objective To investigate the spectrum of BRCA1/BRCA2 mutations in a set of families originary from the Central--Eastern part of Tuscany and to ascertain the presence of founder effects. We also wanted to approximate the age of the most frequent BRCA1 founder mutation. Results Overall, four distinct BRCA1 mutations accounted for a large fraction (72.7%) of BRCA1-attributable hereditary breast/ovarian cancer in families originary from this area. We identified common haplotypes for two newly recognised recurrent BRCA1 mutations, c.3228_3229delAG and c.3285delA. The c.3228_3229delAG mutation was estimated to have originated about 129 generations ago. Interestingly, male breast cancer cases were present in 3 out of 11 families with the c.3228_3229delAG mutation. Conclusions The observation that a high proportion of families with BRCA1 alterations from Central--Eastern Tuscany harbours a limited number of founder mutations can have significant impact on clinical management of at risk subjects from this area. In addition, the identification of a large set of families carrying an identical mutation that predisposes to breast and ovarian cancer provides unique opportunities to study the effect of other genetic and environmental factors on penetrance and disease phenotype. Author Affiliation: (1) Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy (2) Molecular and Nutritional Epidemiology Unit, ISPO-Scientific Institute of Tuscany, Florence, Italy (3) Senology Unit, ISPO-Scientific Institute of Tuscany, Florence, Italy (4) Dipartimento di Medicina Sperimentale, Universita "La Sapienza", Rome, Italy (5) Prevenzione e Salute, PRE.SA, Florence, Italy (6) Fiorgen Foundation for Pharmacogenomics, Sesto Fiorentino, Florence, Italy Article History: Registration Date: 05/09/2008 Received Date: 13/08/2008 Accepted Date: 05/09/2008 Online Date: 27/09/2008