Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.

AIMS: To analyse the frequency of loss of heterozygosity (allele loss, LOH) in a large sample of colorectal carcinomas using highly informative markers along chromosome 11q. METHODS: One hundred paired samples of colorectal cancer and normal tissue were genotyped at six microsatellite markers on chr...

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Main Authors: Tomlinson, I, Bodmer, W
Format: Journal article
Language:English
Published: 1996
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author Tomlinson, I
Bodmer, W
author_facet Tomlinson, I
Bodmer, W
author_sort Tomlinson, I
collection OXFORD
description AIMS: To analyse the frequency of loss of heterozygosity (allele loss, LOH) in a large sample of colorectal carcinomas using highly informative markers along chromosome 11q. METHODS: One hundred paired samples of colorectal cancer and normal tissue were genotyped at six microsatellite markers on chromosome 11q (cen-D11S1313-D11S901-DRD2/NCAM-D11S29- D11S968-tel). The high levels of heterozygosity at these markers allow allele loss to be determined in about 80% of cases at any one locus. The frequency of replication errors (RERs, microsatellite instability) has also been determined. RESULTS: LOH was found at frequencies of 25% and 29% at the distal D11S968 (11qter) and D11S29 (11q23.3) loci, slightly above the accepted baseline of 0-20%. Allele loss at NCAM, DRD2, D11S901, and D11S1313 was not raised above baseline levels. The probable genetic mechanism of allele loss--chromosomal non-disjunction, mitotic recombination, deletion, or gene conversion--seemed to vary between tumours and no consistent mechanism of mutation was found. Microsatellite instability was found in 23 (23%) tumours. No associations were found between LOH and clinical data (patient sex, age at presentation, tumour site, and Duke's stage). CONCLUSIONS: Although gene(s) on 11q may have a role in the development of a minority of colorectal carcinomas, this study provides evidence against the general importance of allele loss on chromosome 11q in the pathogenesis of colorectal cancer. The results also have implications for the importance of 11q in other cancers: it seems less likely that a single tumour supressor gene at this location promotes the growth of all types of tumour when lost. Rather, one or more genes with tissue specific effects may be involved.
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spelling oxford-uuid:a45b0fae-96df-4890-864a-0092382cce0f2022-03-27T02:33:17ZChromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a45b0fae-96df-4890-864a-0092382cce0fEnglishSymplectic Elements at Oxford1996Tomlinson, IBodmer, WAIMS: To analyse the frequency of loss of heterozygosity (allele loss, LOH) in a large sample of colorectal carcinomas using highly informative markers along chromosome 11q. METHODS: One hundred paired samples of colorectal cancer and normal tissue were genotyped at six microsatellite markers on chromosome 11q (cen-D11S1313-D11S901-DRD2/NCAM-D11S29- D11S968-tel). The high levels of heterozygosity at these markers allow allele loss to be determined in about 80% of cases at any one locus. The frequency of replication errors (RERs, microsatellite instability) has also been determined. RESULTS: LOH was found at frequencies of 25% and 29% at the distal D11S968 (11qter) and D11S29 (11q23.3) loci, slightly above the accepted baseline of 0-20%. Allele loss at NCAM, DRD2, D11S901, and D11S1313 was not raised above baseline levels. The probable genetic mechanism of allele loss--chromosomal non-disjunction, mitotic recombination, deletion, or gene conversion--seemed to vary between tumours and no consistent mechanism of mutation was found. Microsatellite instability was found in 23 (23%) tumours. No associations were found between LOH and clinical data (patient sex, age at presentation, tumour site, and Duke's stage). CONCLUSIONS: Although gene(s) on 11q may have a role in the development of a minority of colorectal carcinomas, this study provides evidence against the general importance of allele loss on chromosome 11q in the pathogenesis of colorectal cancer. The results also have implications for the importance of 11q in other cancers: it seems less likely that a single tumour supressor gene at this location promotes the growth of all types of tumour when lost. Rather, one or more genes with tissue specific effects may be involved.
spellingShingle Tomlinson, I
Bodmer, W
Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title_full Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title_fullStr Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title_full_unstemmed Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title_short Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
title_sort chromosome 11q in sporadic colorectal carcinoma patterns of allele loss and their significance for tumorigenesis
work_keys_str_mv AT tomlinsoni chromosome11qinsporadiccolorectalcarcinomapatternsofallelelossandtheirsignificancefortumorigenesis
AT bodmerw chromosome11qinsporadiccolorectalcarcinomapatternsofallelelossandtheirsignificancefortumorigenesis