Screening for BRCA2 mutations in 81 Dutch breast-ovarian cancer families

We have analysed 81 families with a history of breast and/or ovarian cancer for the presence of germline mutations in BRCA2 with a number of different mutation screening techniques. The protein truncation test (PTT) for exons 10 and 11 detected four different frame-shifting mutations in six of these families. Four of the remaining 75 families had given positive linkage evi dence for being due to BRCA2. In these families the entire coding region wa s analysed by single-strand conformational polymorphism, leading to the det ection of a non-sense and a splice-site mutation in two of them. While thes e studies were in progress, Southern analysis of BRCA1 revealed that in our study-population of 81 families. 15 families were segregating either the e xon 13 or exon 22 deletion in BRCA1 (Petrij-Bosch et al (1997) Nat Genet 17 , 341-345). This prompted us to examine BRCA2 in the remaining 58 families by Southern analysis, using two different restriction enzymes. No aberratio ns were found in the restriction patterns. Thus, contrary to BRCA1, large g enomic rearrangements within the BRCA2 gene do not represent a major mutati on mechanism among Dutch breast cancer families. (C) 2000 Cancer Research C ampaign.