Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome

TLDR

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder marked by multiple basal cell carcinomas, palm/sole pits, jaw keratocysts, various tumors, and developmental anomalies, and is linked to chromosome 9q22.3 where loss of heterozygosity suggests a tumor‑suppressor gene. The study proposes that decreased expression of the patched gene causes the syndrome’s developmental defects and that complete loss drives malignant transformation of certain cell types. The authors isolated a human PTC sequence homologous to Drosophila patched from a YAC and cosmid contig spanning the NBCCS locus. Mutation analysis identified alterations in PTC in NBCCS patients and associated tumors.

Abstract

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), pits of the palms and soles, jaw keratocysts, a variety of other tumors, and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Familial and sporadic BCCs display loss of heterozygosity in this region, consistent with the gene being a tumor suppressor. A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, patched, was isolated from a YAC and cosmid contig of the NBCCS region. Mutation analysis revealed alterations of PTC in NBCCS patients and in related tumors. We propose that a reduction in expression of the patched gene can lead to the developmental abnormalities observed in the syndrome and that complete loss of patched function contributes to transformation of certain cell types.