DELETION MAPPING IN COLORECTAL-CANCER OF A PUTATIVE TUMOR SUPPRESSOR GENE IN 8P22-P21.3

Although previous studies of acquired loss of heterozygosity (LOH) in colorectal tumours have suggested that a tumour suppressor gene may li e within the short arm of chromosome 8, its precise localisation remai ns to be determined. To obtain a more accurate positional map 120 colo rectal cancers were examined with eight chromosome 8 polymorphic marke rs comprising both restriction fragment length polymorphisms and micro satellite polymorphisms based on (CA)n repeats. 91 cases were informat ive and LOH was detected in 47 (51%). The markers most commonly sited within the lost region mapped to the lipoprotein lipase gene (LPL) at chromosome 8p22. From study of tumours showing break-points within 8p, a common region of deletion was established extending centromerically from LPL to the ankyrin 1 gene (ANK1) which is mapped to 8p21.1-11.2. This overlaps with common deleted regions observed in other studies o f colorectal tumours (8p23.1-p21.3) and bladder tumours (8p21-q11.2). Taken together, the results in colorectal cancer delineate a region in 8p22-p21.3 where the putative tumour suppressor gene must lie. The ch romosome 8p deletions appear to be independent of those involving 5q a nd 17p in the same tumours. No relationship was found between the pres ence of 8p deletion and site or stage of the tumour, or the sex or age of the patient at diagnosis.