DELINEATION OF 2 DISTINCT DELETED REGIONS ON CHROMOSOME-9 IN HUMAN NONMELANOMA SKIN CANCERS

The mapping of the naevoid basal cell carcinoma syndrome (NBCCS) and t he Ferguson-Smith syndrome to the same region on chromosome arm 9q has led to speculation that the two conditions may reflect different muta tions within the same gene. Loss of heterozygosity of 9q alleles in bo th familial and sporadic basal cell carcinomas (BCCs) suggests that th e NBCCS gene on 9q is acting as a tumour suppressor gene. Although LOH of 9q markers has not been studied in squamous cell neoplasms from pa tients with the Ferguson-Smith syndrome, chromosome 9 allele loss has been reported in sporadic squamous cell carcinomas (SCCs) of the skin. In order to characterise further the deleted region on chromosome 9 i n BCCs and SCCs of the skin we have examined a series of non-melanoma skin cancers using a panel of highly informative microsatellite marker s. Forty-four BCCs and 49 SCCs were studied. Loss of heterozygosity of one or more 9q markers was seen in 33 of the 44 BCCs. Only 4 of the 3 3 BCCs with 9q loss showed loss of 9p markers. Twenty-two BCCs showed loss of all informative 9q markers. Partial or interstitial 9q deletio ns were seen in 5 BCCs, and in 3 of these 5 BCCs the breakpoint occurr ed within the currently defined NBCCS locus. Chromosome 9 loss was see n in 16 of 49 SCCs. In contrast to the low frequency of 9p loss in BCC s, LOH of 9p markers was a common finding in SCCs, occurring in 15 of the 16 SCCs with chromosome 9 loss. In 5 SCCs 9p loss occurred with re tention of 9q alleles. The different patterns of chromosome 9 loss in BCCs and SCCs and the failure to detect loss of markers at the Ferguso n-Smith/NBCCS locus in 5 of 7 informative SCCs with partial chromosome 9 losses suggest that the targets for allelic deletion on chromosome 9 in BCCs and SCCs are different. (C) 1994 Wiley-Liss, Inc.