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 human cancers have suggested the presence of one or more tumor suppressor genes in this region. Furthermore, a genetic locus responsible for familial focal nonepidermolytic palmoplantar keratoderma, a condition associated with cancer of the esophagus, lies in the same region. This esophageal-cancer susceptibility 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 lines for alterations in the expression of transcripts from this portion of 17q, we identified a novel gene that we designated DMC1 (downregulated in multiple cancer-1). The full-length cDNA is 3293bp long. Its putative product is an integral membrane protein of 788 amino acids, belonging to the class of so-called 'inside-out" membrane proteins; it lacks a signal sequence but contains an N-terminal cytoplasmic domain, a single transmembrane peptide, 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 lines, 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 the DMC1 gene at 17q25.1 may play an important role in the development of cancers in a broad range of human tissues.
Harada
H
H
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Japan.
Nagai
H
H
Tsuneizumi
M
M
Mikami
I
I
Sugano
S
S
Emi
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002886:Chromosomes, Human, Pair 17; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C074556:DMC1 protein, human