Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1835664 (TOC)
 2,763 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Identification of DMC1, a novel gene in the TOC region on 17q25.1 that shows loss of expression in multiple human cancers. 1128 19

The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25, a region frequently deleted in sporadic squamous cell oesophageal tumours. Further haplotype analysis described here, based on revised maps of marker order, has reduced the TOC minimal region to a genetic interval of 2 cM limited by the microsatellite markers D17S785 and D17S751. Partial sequence data and complete physical maps estimate the actual size of this region to be only 0.5 Mb. This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1). Computer analysis of sequence data from the minimal region identified 13 candidate genes and the presence of 50-70 other 'gene fragments' as ESTs and/or predicted exons and genes. Ten of the characterized genes were assayed for mutations but no disease-specific alterations were identified in the coding and promoter sequences. This region of chromosome 17q25 is, therefore, relatively gene-rich, containing 13 known and possibly as many as 50 predicted genes. Further mutation analysis of these predicted genes, and others possibly residing in the region, is required in order to identify the elusive TOC locus.
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PMID:Characterization of a 500 kb region on 17q25 and the exclusion of candidate genes as the familial Tylosis Oesophageal Cancer (TOC) locus. 1221 81