1891P - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in the Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers

Abstract

BackgroundFounder BRCA1/2 cancer predisposing mutations have been reported in Italian population. We reported the founder BRCA1 mutation, c.4117G>T - p.Glu1373*, recurring in unrelated families of Abruzzo and Lazio regions of Central Italy. MethodsPreliminary analysis of 17 unrelated families carrying BRCA1 c.4117G>T nonsense mutation reported in the Hereditary Breast/Ovarian Cancer Registry of the Oncology Territorial Care Unit, University of L’Aquila and Genetic Unit, Catholic University of Rome was performed by genetic counselling and peripheral blood collection after written informed consent from affected and unaffected probands. BRCA1/2 genetic analysis were performed by direct sequencing; haplotype analysis was carried out using microsatellite markers in the 17q21 region: D17S846, D17S1328, D17S855 (intragenic), D17S902, D17S806. Post-test genetic counselling was performed to address Therapeutic and/or Preventive Clinical strategies. Geographic area of origin, cancer family trees, cancers affecting the probands were collected. To date, overall 23 unrelated families were enrolled. ResultsIn the preliminary analysis, BRCA1 c.4117G>T mutation was identified in 17 unrelated families with familial origin in a territory of Central Italy including Abruzzo and Lazio regions: this mutation was always and significantly associated with the Allelic Variant (AV) BRCA1, c.3119G>A (p.Ser1040Asn), in 52 tested carriers, 20 affected and 32 unaffected. Microsatellite markers confirmed a common haplotype shared by the 52 probands, comprising the region between D17S1328 and D17S902 markers. In overall 23 unrelated families, the association of BRCA1 founder mutation and the AV were identified in 66 tested carriers, 28 affected and 38 unaffected. ConclusionsThe BRCA1 c.4117G>T is a founder mutation prevalent in the territory of Central Italy in Abruzzo and southern Lazio regions, cosegregating with AV BRCA1 c.3119G>A, providing faster identification of affected and unaffected carriers to specifically address therapeutic and preventive clinical pathways for breast, ovarian and BRCA1-related cancers. Legal entity responsible for the studyEnrico Ricevuto. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.