Spectrum of BRCA1/2 point mutations and genomic rearrangements in high-risk breast/ovarian cancer Chilean families
The distribution of BRCA1/2 germline mutations in breast/ovarian cancer (BC/OC) families varies among different populations. In the Chilean population, there are only two reports of mutation analysis of BRCA1/2 , and these included a low number of BC and/or OC patients. Moreover, the prevalence of B...
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Veröffentlicht in: | Breast cancer research and treatment 2011-04, Vol.126 (3), p.705-716 |
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Zusammenfassung: | The distribution of
BRCA1/2
germline mutations in breast/ovarian cancer (BC/OC) families varies among different populations. In the Chilean population, there are only two reports of mutation analysis of
BRCA1/2
, and these included a low number of BC and/or OC patients. Moreover, the prevalence of
BRCA1/2
genomic rearrangements in Chilean and in other South American populations is unknown. In this article, we present the mutation-detection data corresponding to a set of 326 high-risk families analyzed by conformation-sensitive gel electrophoresis and heteroduplex analysis. To determine the contribution of
BRCA1/2
LGRs in Chilean BC patients, we analyzed 56 high-risk subjects with no pathogenic
BRCA1/2
point mutations. Germline
BRCA1
/
2
point mutations were found in 23 (7.1%) of the 326 Chilean families. Families which had at least three BC and/or OC cases showed the highest frequency of mutations (15.9%). We identified 14 point pathogenic mutations. Three recurrent mutations in
BRCA1
(c.187_188delAG, c.2605_2606delTT, and c.3450_3453delCAAG) and three in
BRCA2
(c.4969_4970insTG, c.5374_5377delTATG, and c.6503_6504delTT) contributed to 63.6 and 66.7% of all the deleterious mutations of each gene, which may reflect the presence of region-specific founder effects. Taken together
BRCA1/2
recurrent point mutations account for 65.2% (15/23) of the
BRCA1/2
(+) families. No large deletions or duplications involving
BRCA1
/
2
were identified in a subgroup of 56 index cases negative for
BRCA1/2
point mutations. Our study, which is the largest conducted to date in a South American population, provides a comprehensive analysis on the type and distribution of
BRCA1/2
mutations and allelic variants. |
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ISSN: | 0167-6806 1573-7217 |
DOI: | 10.1007/s10549-010-1170-y |