High frequency of BRCA recurrent mutations in a consecutive series of unselected ovarian cancer patients

Abstract

Hereditary predisposition to breast and ovarian cancer (HBOC) is diagnosed by molecular analysis of deleterious mutations in BRCA genes, allowing oncogenetic follow-up of patients and of their families. BRCA testing addresses only to HBOC families, using restrictive inclusion criteria based on familial history of cancer and age at diagnosis. Sporadic ovarian cancer has high incidence and mortality in Romania, with low median age of diagnosis and possibly a higher magnitude of hereditary contribution comparing to othe populations. However, sporadic ovarian cancers do not qualify for BRCA testing according to inclusion criteria, and a complete BRCA screening of all cancers is neither feasible nor recommended. Despite the large diversity of BRCA mutations worldwide, some recurrent mutations have higher frequencies in diverse populations. Precisely screening for recurrent mutations in a target population allows to rapidly identifying mutation carriers without sequencing the entire BRCA genes. In Romanian population and neighboring countries, several recurrent mutations have already been described. In a consecutive series of 50 sporadic ovarian cancer patients, not qualifying for BRCA complete testing, we screened for 9 most common BRCA mutations, by multiplex-PCR, RFLP and targeted Sanger sequencing. Our results revealed 6 different BRCA mutations in 8 unrelated patients, with a frequency of 16%, much higher than expected. We further recommend screening for the identified mutations in larger series of cancer patients. The results are highly beneficial to cancer patients, healthy relatives, and overall, considering prevention in cancer a priority, to public health system and future of oncogenetics in Romania

Spectrum of BRCA1/2 Mutations in Romanian Breast and Ovarian Cancer Patients

“…The BRCA2 mutation c.8680C>T (chr13:32950854) has also been previously described in the Romanian population and, in our analysis, it was associated with early onset of BC (36 years) [ 22 ].…”

“…These latter two mutations (c.181T>G and c.1687C>T) represent the main BRCA1 mutations in the Slovenian population with a frequency of 56% and 30%, respectively, and they are also found in South-Eastern Europe (Greece in particular) [ 21 ]. c.1687C>T also represents a common mutation prevalent in other European countries such as Austria and Sweden with a common founder ancestor [ 22 ].…”