LOW PROPORTION OF BRCA1 AND BRCA2 MUTATIONS IN FINNISH BREAST-CANCER FAMILIES - EVIDENCE FOR ADDITIONAL SUSCEPTIBILITY GENES

One hundred breast and breast-ovarian cancer families identified at th e Helsinki University Central Hospital in southern Finland and previou sly screened for mutations in the BRCA2 gene were now analyzed for mut ations in the BRCA1 gene. The coding region and splice boundaries of B RCA1 were analyed by protein truncation test (PTT) and heteroduplex an alysis (HA)/SSCP in all 100 families, and 70 were also screened by dir ect sequencing. Contrary to expectations based on Finnish population h istory and strong founder effects in several monogenic diseases in Fin land, a wide spectrum of BRCA1 and BRCA2 mutations was found. In the B RCA1 gene, 10 different protein truncating mutations were found each i n one family. Six of these are novel Finnish mutations and four have b een previously found in other European populations. Six different BRCA 2 mutations were found in 11 families. Altogether only 21% of the brea st cancer families were accounted for by mutations in these two genes. Linkage to both chromosome 17q21 (BRCA1) and 13q12 (BRCA2) was also e xcluded in a subset of seven mutation-negative families with four or m ore cases of breast or ovarian cancer. These data indicate that additi onal breast and breast-ovarian cancer susceptibility genes are likely to be important in Finland.