BRCA1 and BRCA2 mutation analysis in breast cancer families from Sardinia

G Palomba PhD^a, M Pisano PhD^a, A Cossu MD^b, MF Dedola MD^c, A Farris MD^d, A Contu MD^e, MP Satta, S Tech^a, MC Sini PhD^a, PP Demuro PhD^a, C Rozzo PhD^a, M Casula PhD^a, M Colombino PhD^a, A Manca PhD^a, P Baldinu PhD^a, AA Carboni MD^b, A Deiana MD^b, F Tanda MD^b, G Palmieri MD^a

^aICB-CNR, Alghero, Sassari, ^bInstitute of Pathology, University of Sassari, A.S.L.1, Sassari, ^cDept. of Radiotherapy, ^dMedical Oncology; University of Sassari, A.S.L.1, Sassari, ^eDept. of Medical Oncology, A.S.L.1, Sassari, Italy

AIM: Genetically homogeneous Sardinian population can be helpful in defining the molecular basis of cancer. To evaluate the incidence of disease-causing mutations in breast cancer (BC) families from Sardinia we screened the two major BC susceptibility genes, BRCA1 ad BRCA2, and correlated the presence of mutations with clinicopathological parameters. METHODS: Using a combination of screening screening approaches (SSCP, DHPLC, and automated sequencing), 101 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. RESULTS: Two BRCA1/2 germline sequence were identified. BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in thirteen families (13%). BRCA2-8765delAG was found in 11/13 (85%) BRCA1/2-positive families and 26/659 (4%) unselected and consecutively collected BC patients from the same geographical area. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P<0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. CONCLUSIONS: Identification of such features should address BC patient and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this represents a comprehensive study of the prevalence of BRCA1/2 germline mutations in Sardinia, having immediate implications for the clinical management of BC families.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 896 (Tumor suppressor genes).