SCREENING FOR MUTATIONS IN EXON-11 OF THE BRCA1 GENE IN 70 ITALIAN BREAST AND OVARIAN-CANCER PATIENTS BY PROTEIN TRUNCATION TEST

The most common mutations in the familial breast and ovarian cancer su sceptibility gene BRCA1 are frameshift and nonsense mutations, which l ead to the synthesis of truncated proteins. On this ground, we have an alysed BRCA1 exon 11, which includes about 61% of coding region, in ge rmline DNA from 70 Italian breast and/or ovarian cancer patients, usin g the protein truncation test (PTT). BRCA1 mutations were identified i n nine of 29 (similar to 31%) patients with a family history of cancer and in three of 41 (similar to 7%) women with early-onset breast carc inomas, and were subsequently characterized by sequence analysis. In a ddition, BRCA1 mutations were also detected in six affected relatives of two positive index cases, The observed frequencies of mutations wer e not significantly different from those expected on the basis of the phenotypic characteristics of patients and their families, indicating that PTT is a rapid and sensitive method that can be used for a first BRCA1 mutational screening, The histological findings in BRCA1 mutated cases showed that eight of nine (similar to 89%) breast carcinomas we re of grade III and nine of 9 (100%) ovarian carcinomas were of the en dometrioid type (eight of grade III and one of grade II). This suggest s that specific histological characteristics may represent additional criteria for selection of cases eligible to BRCA1 mutational analysis.