Fine deletion mapping on the long arm of chromosome 9 in sporadic and familial basal cell carcinomas.

Basal cell carcinomas (BCCs) are the most common sporadic cancers worldwide. They are also a cardinal manifestation of a familial cancer predisposition syndrome, naevoid BCC syndrome (NBCCS). The gene responsible for NBCCS is likely to be a tumour suppressor gene and has been genetically mapped to a 2cM region between microsatellite markers, D9S196 and D9S180 at 9q22.3-q31. 101 BCCs (63 sporadic and 38 familial) were examined for loss of heterozygosity (LOH) in the candidate region of the NBCCS gene. Deletions were found in 46% and all LOH is consistent with genetic mapping of the NBCC locus. These findings strongly support the hypothesis that inactivation of the putative tumour suppressor, the NBCCS gene, is important in the formation of sporadic BCCs. One sporadic tumour indicates that the smallest region of overlap of these deletions is within the interval between D9S287 and D9S180. If this is confirmed in additional tumours, it would further narrow down the NBCCS region and exclude one candidate gene, that for the C complementation group of Fanconi anaemia, which maps proximally to D9S287. However, it would not exclude another candidate, the gene for the A complementation group of xeroderma pigmentosum (XPAC). Evidence of imprinting was also sought but preliminary data indicate that it is unlikely to occur at the NBCCS locus.