Germline BRCA1 alterations in a population-based series of ovarian cancer cases

Citation
Sa. Janezic et al., Germline BRCA1 alterations in a population-based series of ovarian cancer cases, HUM MOL GEN, 8(5), 1999, pp. 889-897
Citations number
34
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN MOLECULAR GENETICS
ISSN journal
0964-6906 → ACNP
Volume
8
Issue
5
Year of publication
1999
Pages
889 - 897
Database
ISI
SICI code
0964-6906(199905)8:5<889:GBAIAP>2.0.ZU;2-D
Abstract
The objective of this study was to provide more accurate frequency estimate s of breast cancer susceptibility gene 1 (BRCA1) germline alterations in th e ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian ca ncer cases. This is the first population-based ovarian cancer study reporti ng BRCA1 alterations derived from a comprehensive screen of the entire codi ng region. One hundred and seven ovarian cancer cases were analyzed for BRC A1 alterations using the RNase mismatch cleavage assay followed by direct s equencing. Two truncating mutations, 962del4 and 3600del11, were identified . Both patients had a family history of breast or ovarian cancer. Several n ovel as well as previously reported uncharacterized variants were also iden tified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Cau casian cancer cases in this series and 24 sister controls using allele-spec ific amplification, The rare form of the Q356R polymorphism was significant ly (P = 0.03) associated with a family history of ovarian cancer, suggestin g that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of po lymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population.