Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy

Maurizio Genuardi, Laura Papi, Anna Laura Putignano, Caterina Congregati, Ines Zanna, Francesco Sera, Doralba Morrone, Mario Falchetti, Marco Rosselli Del Turco, Laura Ottini, Domenico Palli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

24 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)497-504
Numero di pagine8
RivistaBreast Cancer Research and Treatment
Volume117
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • BRCA2 MUTATION
  • CARRIERS
  • FAMILIES
  • FREQUENCY
  • GENES
  • IDENTIFICATION
  • MALE BREAST-CANCER
  • OVARIAN-CANCER
  • PREVALENCE
  • RISK

Fingerprint

Entra nei temi di ricerca di 'Founder mutations account for the majority of BRCA1-attributable hereditary breast/ovarian cancer cases in a population from Tuscany, Central Italy'. Insieme formano una fingerprint unica.

Cita questo