Detailed deletion mapping of chromosome segment 17q12‐21 in sporadic breast tumours

Abstract

Linkage studies have indicated that a gene on chromosome arm 17q, designated BRCA1, confers susceptibility to familial breast and ovarian cancer. To investigate the possible involvement of the BRCA1 gene in sporadic breast cancer we have analysed loss of heterozygosity (LOH) in a panel of 100 sporadic primary breast tumours using 10 PCR-based polymorphic markers from 17q12-21. Allele losses were detected in 40 of 100 tumours informative for at least one of the markers analysed. Of these 40 deleted tumours, 27 showed partial or interstitial loss on 17q. The pattern of LOH in the tumours with partial or interstitial LOH revealed three putative distinct deleted regions on 17q12-21. The first lies on the proximal long arm between D17S250 and THRA1; the second one lies between D17S776 and D17S579, the region containing the BRCA1 gene; and the third is telomeric to D17S733. The most frequently deleted region overlaps with the minimal region containing the BRCA1 gene, suggesting that this gene might also be associated with the development or progression of a proportion of sporadic breast tumours.

Analysis of the 10q23 chromosomal region and the PTEN gene in human sporadic breast carcinoma

“…LOH analyses of a larger population of sporadic breast tumours may help to clarify this issue. The loss of multiple distinct regions on chromosome 10 may be analogous to the situation on chromosome 17 in sporadic breast tumours, in which at least five distinct deleted regions have been recognized (Nagai et al, 1994(Nagai et al, , 1995. In the case of chromosome 17, the pattern of LOH is significantly correlated with some clinical parameters of the breast tumours (Bevilacqua et al, 1989;Nagai et al, 1995;Midulla et al, 1996).…”

Identification of DMC1, a novel gene in the TOC region on 17q25.1 that shows loss of expression in multiple human cancers

“…Three or four distinct regions of deletion on 17q have been identified in sporadic breast cancers (Cropp et al 1993;Nagai et al 1994;Kalikin et al 1996;Niederacher et al 1997;Plummer et al 1997). Mutations of the BRCA1 gene at 17q21 are responsible for predisposition to a hereditary syndrome of breast/ovarian cancer.…”

Understanding Germ-Line Mutations inBRCA1

“…47 Loss of heterozygosity (LOH) of the wild-type BRCA1 allele occurs in up to 86% of tumors in BRCA1 mutation carriers, and in ~30% of sporadic tumors. [48][49][50] Further confirmation of this possibility must await a systematic study of the mechanisms for LOH in human breast and ovarian carcinomas.…”