Refinement of the LOH region 1 at 11q23.1 deleted in human breast carcinomas and sublocalization of 11 expressed sequence tags within the refined region

Abstract

Loss of constitutive heterozygosity at 11q23 has been detected in various human solid tumors. Here, we described the analysis of a series of normal and tumor pairs from 110 breast carcinomas for the presence of loss of heterozygosity at 11q23 loci. The overall frequency of LOH was 48%, con®rming the importance of deletions at 11q23 in breast tumorigenesis. Previously, we have identi®ed two independent regions of LOH at 11q23, the LOH region 1 at 11q23.1 and the LOH region 2 at 11q23.3. The most telomeric region was recently re®ned between loci D11S1345 and D11S1316, a region of about 1 Mb. However, the LOH region 1, most centromeric, was still not ®nely re®ned: the boundaries were de®ned by loci D11S2000 and D11S897, separated by about 8 Mb. Here, we re®ned its boundaries between loci D11S1347 and D11S927, a region of about 2 Mb. We have mapped 11 expressed sequence tags (ESTs) within this region and excluded another 20. This study represents a further step toward the identi®cation of the putative tumor suppressor gene found within the LOH region 1 at 11q23.1.Keywords: LOH at 11q23; breast cancer Loss of heterozygosity studies are believed to pinpoint the location of cancer recessive genes, and several studies have indicated that the long arm of chromosome 11 harbors genes that are deleted during tumorigenesis. Deletions at 11q23 were detected in a variety of human neoplasms, including breast (Carter et al

A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region

“…However, until ordered, gapfree and fully-annotated genomic sequences are available for each chromosome, high-resolution, informative physical maps, especially in regions of biological interest, should continue to be useful by complementing raw sequence data. Three mega-YAC-based physical maps spanning this region of chromosome 11q23 have been previously reported, 21,32,33 however they do not provide detailed coverage for the interval presented in this study. The abundance of transcripts and the presence of three NotI sites within an approximate 1.1-Mb interval indicate a gene-rich genomic domain around the SDHD gene.…”

MicroRNAs and chromosomal abnormalities in cancer cells

“…For example, in breast carcinomas two different regions of loss at 11q23, independent from ataxia telangiectasia-mutated (ATM) locus have been studied extensively: the first spans about 2 Mb between loci D11S1347-D11S927, the second is located between loci D11S1345-D11S1316 and is estimated at about 1Mb (di Iasio et al, 1999). Candidate TSG(s) were not found in spite of extensive effort, except the PPP2R1B (protein phosphatase 2, regulatory subunit A, beta isoform) gene, involved in o10% of cases (Wang et al, 1998;Calin et al, 2002).…”

The 13q and 11q B‐cell chronic lymphocytic leukaemia‐associated regions derive from a common ancestral region in the zebrafish

“…Contained within this is the smaller common overlapping region of deletion between D11S2106 and D11S966E (2AE7 Mb). The larger deletion is also a common region of loss in other cancers including breast (di Iasio et al, 1999;Laake et al, 1999), lung (Wang et al, 1999), ovary , melanoma (Herbst et al, 1999) and oral carcinomas (Hui et al, 1996).…”

“…2001; Elnenaei et al, 2003) and solid malignancies (Gupta et al, 1999;Herbst et al, 1999;di Iasio et al, 1999;Koike et al, 1999;Laake et al, 1999;Wang et al, 1999;Yin et al, 1999;Latil et al, 2002). At 13q14, a consensus region of deletion with an approximate size of 600 kb between D13S273 and D13S25 has been described (Kitamura et al, 2000;Bullrich et al, 2001;Mabuchi et al, 2001;Migliazza et al, 2001;Wolf et al, 2001), although various reports have described smaller internal regions, based largely on the observations from one or two cases (Kalachikov et al, 1997;Liu et al, 1997;Corcoran et al, 1998;Stilgenbauer et al, 1998).…”