[Molecular study of the BRCA1 and BRCA2 genes in 153 breast cancer families from Castilla and León (Spain): new nine unclassified variants identified]

Abstract

Background: It is estimated that 5-10% of breast cancers have an hereditary origin, germline mutations of BRCA1 and BRCA2 genes causing a predisposition. In the present study we analyzed BRCA1 and BRCA2 mutations in moderate to high risk breast cancer patients in order to find out the types and frequency of these mutations in the Spanish regional community of Castilla y León.

Patients and method: We studied 207 moderate to high risk patients from 153 selected families. Genomic DNA was extracted from peripheral blood and analyzed by multiplex polymerase chain reaction-heteroduplexes-conformation sensitive gel electrophoresis (multiplex PCR-HA-CSGE). All variants detected were sequenced to further verify the mutation.

Results: 45 alterations (23 in BRCA1 and 22 in BRCA2) were identified in 74 families (48.4%), corresponding to 13 polymorphisms (29 families), 19 unclassified variants (26 families) of which 9 have not been previously described and 13 cancer-prone mutations (19 families; 12.42% of all families). Eight out of the 19 deleterious mutations (42.1%) were detected in the BRCA1 gene and 11 (57.9%) in the BRCA2 gene. The most prevalent mutation was 3036delACAA, which was detected in four unrelated families.

Conclusions: The high proportion of mutations, polymorphisms and unclassified variants we have detected may be the result of the sensitive procedure and the risk selection criteria used in this study. There is a high proportion of unclassified variants. Their role in the disease must be clarified through more studies, including their typing in control samples.