BRCA1 andBRCA2 genes: Role in hereditary breast and ovarian cancer in Italy

Abstract

The heritable defects of BRCA1 and BRCA2 genes have been shown to predispose to breast and ovarian cancers. In a previous report, we analyzed 46 Italian families with breast and/or ovarian cancer for BRCA1 mutations. In the present study, those families and 11 others were screened for BRCA2 mutations; the newly enrolled families were also analyzed for the BRCA1 gene. The coding region and splice boundaries of BRCA2 and BRCA1 genes were assessed by the protein‐truncation test and single‐strand conformational polymorphism. A total of 20 different mutations were found in 21 families (37%). A total of 9 families (16%) showed mutations in the BRCA1 gene, including the one new mutation identified in this study (5382insC), and 12 families (21%) presented mutations in the BRCA2 gene. BRCA2‐mutated families presented breast and ovarian cancers or breast cancers only, whereas most BRCA1‐mutated families presented ovarian cancer alone or in association with breast cancer. All the BRCA2 mutations led to a truncated protein: 6 were frameshift mutations, 4 were non‐sense mutations and 2 involved the intronic invariant region leading to splice variants. Therefore, in the Italian population, the cumulative proportion of BRCA1 and BRCA2 mutations was within the range observed in other studies (37%), with higher involvement of BRCA2 than of BRCA1. Many families in which no mutations were found presented a very high incidence of breast and/or ovarian cancer. Among the 36 BRCA1 and BRCA2 wild‐type families, 24 presented at least 4 cancer cases, indicating the existence of other important predisposing genes. Int. J. Cancer 83:5–9, 1999. © 1999 Wiley‐Liss, Inc.

Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

“…16 In all of these studies, the highest frequencies of mutations were identified in family types corresponding to our Groups A and B. For both groups, higher mutation rates were detected in the BRCA1 gene.…”

“…[12][13][14][15] The proportion of cases attributed to BRCA1 ranges from 10% in Finland and the Netherlands to approximately 25% in France and Sweden, BRCA2 mutation detection rates are generally around 10%, with the exception of Italy where germline mutations have been found in 25% of 49 families analyzed. 16 There are to date no comprehensive studies in the German population where most studies have been limited to the analysis of BRCA1 or to relatively small series. [17][18][19][20] In 1996, the Deutsche Krebshilfe supported the formation of a research collaboration, the "German Consortium for Hereditary Breast and Ovarian Cancer," to establish a national network for the management and treatment of women with a familial predisposition to breast and ovarian cancer.…”

BRCA1 and BRCA2 mutations in breast/ovarian cancer patients from central Italy

“…This analysis allowed to detect eight different mutations, with a detection rate of 11.7%. In the two previous studies carried out in Italy by screening the entire BRCA1/BRCA2 sequences, Ottini et al (2000) detected mutations in 8% of 136 Italian patients, while Santarosa et al (1999) disclosed mutations in 37% of cases studying 57 selected Italian families. These different detection rates are clearly due to the different criteria of selection employed, since Santarosa et al (1999) used more stringent criteria of autosomal-dominant predisposition.…”

BRCA2 founder mutation in Slovenian breast cancer families

“…The availability of this highly recurrent mutation may also contribute to the elucidation of the molecular mechanisms responsible for the tissue specificity of particular cancer-linked mutations. The IVS16-2A4G mutation was reported worldwide only three times by the BIC database, twice by Myriad in 'Western Europeans' and once by Dr M Santarosa 13 from Aviano, a city located in Italy at less than 100 km from the Slovenian border. The eastern part of today's Italy and Slovenia were before the First World War part of the Austro-Hungarian empire, and there is still a Slovene minority officially recognized in the eastern part of Italy.…”