FREQUENT LOSS OF HETEROZYGOSITY AT TELOMERIC LOCI ON 22Q IN SPORADIC COLORECTAL CANCERS

To date, several tumor-suppressor genes responsible for the tumorigene sis of colorectal cancer have been identified. However, studies of los s of heterozygosity (LOH) have suggested several chromosomal regions w hich may contain additional tumor-suppressor genes for colorectal canc er. To determine the extent and variation of allelic loss on 22q, on w hich LOH has been frequently observed, a total of 68 sporadic colorect al cancers was examined for LOH on the chromosome arm by means of 16 p olymorphic DNA markers. LOH was observed in 28 tumors (41%), of which 9 showed LOH at all informative loci. The remaining 19 tumors showed v ariable patterns of partial loss on 22q, delimiting the smallest regio n of overlap (SRO) between D22S90 and D22S94. Moreover, LOH within the SRO correlated with a progression in terms of Dukes' stages. These re sults suggest that an additional tumor-suppressor gene for colorectal cancer may exist on 22q distally to the NF2 locus and that inactivatio n of the gene may possibly play a role in the progression or metastasi s of colorectal cancers. (C) 1995 Wiley-Liss, Inc.