Mutations in susceptibility breast/ovarian cancer (BOC) genes show different spectra according to geographic origin. To date, few BRCA1 and BRCA2 mutations are described as founder in Spanish population, intriguingly linked to geographic distribution. Other susceptibility genes that share key roles in Fanconi Anemia pathway are now being scanned for mutations. A total of 1275 unrelated families have been tested for BRCA mutations in the IBGM. Samples and written informed consent of BOC cases and relatives were collected at the Genetic Counselling Units of East CyL. DNA was scrutinized for BRCA mutations by HA-CAE and subsequently sequence analysis of abnormal patterns. Additionally, MLPA was performed in high-risk patients with familial history of BOC without point mutations. Moreover, other genes as PALB2 or RAD51C were tested in families with specific cancer features. Seventy-four different deleterious DNA changes in BRCA genes have been identified in our laboratory in 186 unrelated families (69 BRCA1+ and 117 BRCA2+ families). Spanish founder mutations were predominant in our samples: 330A>G, 5242C>A and 5272-1G>A in BRCA1 and 3036_3039delACAA, 5374_5377delTATG and 9254_9258delATCAT in BRCA2. Remarkably, 187_188delAG-BRCA1 mutation was absent in our region. Five different large rearrangements in seven ovarian unrelated patients have been detected during MLPA analysis. No pathological mutations were identified in either RAD51C or PALB2. Our target population shows a particular BRCA1 and BRCA2 mutation spectra where Spanish founder mutations are leading. Although mutations in other susceptibility BOC genes do not yield results so far, comprehensive studies with larger number of samples would be performed.

Resumen del póster presentado a la European Human Genetics Conference celebrada en Nuremberg (Alemania) del 23 al 26 de junio de 2012.

Peer Reviewed