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Loss of heterozygosity (allele loss, LOH) occurs frequently on the long arm of chromosome 11 in several types of cancer. We analysed 32 melanomas (almost all metastatic lesions) for allele loss at eight loci along the length of chromosome 11 (ptel-D11S922-D11S899-D11S1324-D11S1313-++ +D11S901-NCAM-D11S29-D11S968-qtel). The highest frequency of loss (38%) was at D11S29 (11q23.3). Of 13 melanomas which had lost an allele at one or more loci, all but one showed LOH at either D11S29 or NCAM (11q22). The region between these two loci is the most likely location of any tumour suppressor gene. Low frequencies of LOH occurred on 11p and there was little evidence for tumour suppressor loci outside the 11cen-q23.3 region. Unusually for melanomas, widespread microsatellite instability, with slippage of several repeat units, was observed in two of 32 tumours studied (and four other tumours showed new microsatellite alleles that differed by just one repeat unit from their normal counterparts). However, no mutations of the mismatch repair genes hMSH2 and hMLH1 were detected in these two tumours, and the observed replication errors may result from mutations in other genes involved in mismatch repair or DNA replication. LOH on 11q and replication errors appear to comprise part of the genetic pathways of several tumour types, including melanomas.

Original publication

DOI

10.1016/0959-8049(96)00198-0

Type

Journal article

Journal

Eur J Cancer

Publication Date

09/1996

Volume

32A

Pages

1797 - 1802

Keywords

Adult, Aged, Aged, 80 and over, Alleles, Chromosome Deletion, Chromosomes, Human, Pair 11, DNA Replication, DNA, Neoplasm, Humans, Melanoma, Microsatellite Repeats, Middle Aged, Polymorphism, Single-Stranded Conformational