Down-regulation in multiple human cancers of a novel gene, DMHC, from 17q25.1 that encodes an integral membrane protein

Frequent observations of allelic loss in chromosomal band 17q25.1 in a vari ety of human cancers have suggested that one or more tumor suppressor genes are present in that region. Moreover, a genetic locus for hereditary focal non-epidermolytic palmoplantar keratoderma, a condition associated with ca ncer of the esophagus (TOC; Tylosis with Oesophageal Cancer), lies in the s ame region. We screened cell lines derived from a variety of human cancers by reverse transcription-polymerase chain reaction (RT-PCR) to detect alter ations in expression of genes within the region in question, by examining e xpressed sequence tags located there. These experiments identified an 1834- bp full-length cDNA encoding a novel, 441-amino acid integral membrane prot ein with seven putative transmembrane domains. This gene showed loss or ext reme decrease of expression in 6 of 10 uterine cancer-cell lines, 2 of 11 h epatic cell carcinoma-cell lines, 2 of 7 lung cancer-cell lines, 1 of 6 gas tric cancer-cell lines, and 1 of 10 breast cancer-cell lines. (We named it DMHC ("down-regulated in multiple human cancers").) Our results suggest tha t loss of expression of DMHC at 17q25.1 may play an important role in devel opment of variety of human cancers.