MUTATIONS IN THE HUMAN HOMOLOG OF THE DROSOPHILA PATCHED GENE IN ESOPHAGEAL SQUAMOUS-CELL CARCINOMA

The human homologue (PTCH) of the Drosophila segment polarity gene pat ched has recently been identified as a tumor-suppressor gene for nevoi d basal cell carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We analyzed 30 esophageal squamous cell carcinomas (ESCC ) for intrageneic mutations of the PTCH gene by polymerase chain react ion-single-strand conformation polymorphism analysis followed by DNA s equencing. We identified two somatic PTCH mutations (7%) in 30 ESCC. T hese were a nonsense mutation (CAG to TAG at codon 361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of the PTCH gene. These results indicate that inactivation of the PTCH gene via a two-hit mechanism occurs in a subset of ESCC. (C) 1998 Wil ey-Liss, Inc.