Chromosome 11q in sporadic colorectal carcinoma: patterns of allele loss and their significance for tumorigenesis.
OBJECTIVE
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.
Tomlinson
I P
IP
Cancer Genetics Laboratory, Imperial Cancer Research Fund, London.
Bodmer
W F
WF
D000367:Age Factors; D000368:Aged; D002880:Chromosomes, Human, Pair 11; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004261:DNA Replication / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009367:Neoplasm Staging; D012737:Sex Factors