Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast ovarian cancer families

Citation
M. Montagna et al., Identification of a 3 kb Alu-mediated BRCA1 gene rearrangement in two breast ovarian cancer families, ONCOGENE, 18(28), 1999, pp. 4160-4165
Citations number
16
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
09509232 → ACNP
Volume
18
Issue
28
Year of publication
1999
Pages
4160 - 4165
Database
ISI
SICI code
0950-9232(19990715)18:28<4160:IOA3KA>2.0.ZU;2-X
Abstract
Most of the hereditary breast cancers are attributed to constitutive altera tions of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of th ese genes in 'high risk' families are found less frequently than expected f rom linkage data. Recent findings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutati on negative cases. We studied 60 affected probands belonging to families wi th a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis, DNA was analysed by the Sou thern blotting procedure using three different restriction enzymes, and tno probes obtained by RT-PCR of the 5' and 3' BRCA1 coding sequence. A 3 kb d eletion encompassing exon 17 and causing a frameshift mutation was identifi ed in two independently ascertained families. RT-PCR and long-range DNA PCR were employed to characterize the rearrangement that was finally shown to be the result of a recombination between tno very similar Alu repeats. This type of mutation is not identified by the conventional methods of mutation detection which are based on PCR amplification of single exons, Therefore, further search for gene rearrangements is needed to better define the prop ortion of 'high risk' families that might be explained by gross genomic alt erations of the BRCA1 gene.