Identification of DMC1, a novel gene in the TOC region on 17q25.1 that shows loss of expression in multiple human cancers

Frequent allelic losses within chromosomal band 17q25.1 in a variety of hum an cancers have suggested the presence of one or more tumor suppressor gene s in this region. Furthermore, a genetic locus responsible for familial foc al nonepidermolytic palmoplantar keratoderma, a condition associated with c ancer of the esophagus, lies in the same region. This esophageal-cancer sus ceptibility locus, TOC (tylosis with oesophageal cancer), might be a target of deletions at 17q25.1 in multiple types of malignancy. Using the reverse transcriptase-polymerase chain reaction (RT PCR) to examine cancer cell li nes for alterations in the expression of transcripts from this portion of 1 7q, we identified a novel gene that we designated DMC1 (downregulated in mu ltiple cancer-1). The full-length cDNA is 3293 bp long. its putative produc t is an integral membrane protein of 788 amino acids, belonging to the clas s of so-called "inside-out" membrane proteins; it lacks a signal sequence b ut contains an N-terminal cytoplasmic domain, a single transmembrane peptid e, and a C-terminal extracellular domain. We documented loss of expression of DMC1 in 2 of 10 breast-cancer cell lines, in 7 of 10 cervical-cancer lin es, in 7 of 13 hepatocellular-cancer lines, in 3 of 7 lung-cancer lines, in 3 of 6 thyroid-cancer lines, in 2 of 6 gastric-cancer lines, and in 2 of 4 renal cell-cancer lines. Our results suggest that loss of expression of th e DMC1 gene at 17q25.1 may pray an important role in the development of can cers in a broad range of human tissues.