Inscriere cercetatori

Identification of a recurrent BRCA1 mutation in two breast/ovarian cancer predisposition families with distinct phenotypes, by using allele-specific multiplex-PCR

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Lucian Negura, Eugen Carasevici, Anca Negura, Nancy Uhrhammer, Yves-Jean Bignon

Editorial: Romanian Rerview of Laboratory Medicine, 18(2), p.53-61, 2010.


Hereditary predisposition to breast and ovarian cancer is mainly attributable to predisposition genes BRCA1 and BRCA2. Lifetime risk of developing either breast or ovarian cancer is significantly higher for BRCA germ line deleterious mutation carriers compared to the general population. Screening for BRCA mutations is nowadays standard practice in the western world, and allows medical follow-up and genetic counseling for patients. In spite of the large BRCA mutation spectrum, some recurrent mutations are responsible for a large percentage of predisposition families. In Eastern European populations, BRCA1 5382insC is a common recurrent Ashkenazi founder mutation. Patients and methods. We identified and recruited 19 hereditary breast and ovarian cancer (HBOC) families, with at least 3 cases of epithelial breast or ovarian cancer within the same family line. All patients agreed by written informed consent. DNA was extracted from peripheral blood. A particular allele-specific multiplex-PCR method was used to screen for the recurrent 5382insC mutation. Amplification and Sanger sequencing were used to confirm the presence of the mutation. Results. The BRCA1 5382insC mutation was found in two different HBOC families, with different breast/ovarian cancer familial history and without any apparent degree of relatedness. Conclusions. We demonstrated the feasibility of a rapid screening in our population for known recurrent BRCA1 mutations, by using simple PCR-based techniques. This result, the first one in Romania, could open the way for a population study to determine the frequency of 5382insC in the Romanian population. This could also develop the oncogenetic approach and follow-up of BRCA mutations bearers in Romania.

Cuvinte cheie: hereditary breast/ovarian cancer (HBOC), BRCA recurrent mutation, allele-specific multiplex-PCR.