MUTATION ANALYSIS OF THE HUMAN HOMOLOG OF DROSOPHILA PATCHED AND THE XERODERMA-PIGMENTOSUM COMPLEMENTATION GROUP-A GENES IN SQUAMOUS-CELL CARCINOMAS OF THE SKIN

The human homologue of Drosophila patched (PTCH), located at chromosom e 9q22.3, was recently identified as a candidate tumor suppressor gene for familial and sporadic basal cell carcinomas. Squamous cell carcin omas (SCCs) of the skin display allelic loss in this chromosomal regio n, which, in addition to the PTCH gene, contains the DNA repair gene x eroderma pigmentosum complementation group A (XPA). Patients with xero derma pigmentosum are predisposed to non-melanoma skin tumors because of deficient excision repair of ultraviolet-induced DNA damage. Mutati on analysis by single-strand conformation analysis and direct DNA sequ encing of all 23 exons of the PTCH gene and all six exons of the XPA g ene in 14 SCCs did not reveal structural alterations in any of these g enes. Additionally, analysis of PTCH expression by in situ hybridizati on in SCCs revealed no evidence of upregulation of PTCH mRNA, confirmi ng the lack of mutations in this gene. These findings suggest that ano ther, yet to be identified gene or genes on chromosome 9q are involved in SCC tumorigenesis. (C) 1998 Wiley-Liss, Inc.