Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our effort to identify BRCA1, 22 genes were cloned from a 1-Mb region of chromosome 17q21 defined by meiotic recombinants in families with inherited breast and/or ovarian cancer. Subsequent discovery of another meiotic recombinant narrowed the region to approximately 650 kb. Genes were cloned from fibroblast and ovarian cDNA libraries by direct screening with YACs and cosmids. The more than 400 cDNA clones so identified were mapped to cosmids, YACs, and P1 clones and to a chromosome 17 somatic panel informative for the BRCA1 region. Clones that mapped back to the region were hybridized to each other and consolidated into clusters reflecting 22 genes. Ten genes were known human genes, 5 were human homologs of known genes, and 7 were novel. Each gene was sequenced, compared to genes in the databases to find homologies, and analyzed for mutations in BRCA1-linked families and tumors. Eight mutations were found in tumors or families and not in controls. In the gene encoding alpha-N-acetylglucosaminidase, approximately 100 kb proximal to the 650-kb linked region, somatic nonsense, missense, and splice junction mutations occurred in 3 breast tumors, but not in these patients' germline DNA nor in controls. In an ets-related oncogene in the linked region, a missense mutation cosegregated with breast cancer in one family and was not observed in controls. In a human homolog of a yeast pre-mRNA splicing factor, 3 different mutations cosegregated with breast cancer in 3 families and were not observed in controls. In these and the other genes in the region, 36 polymorphic variants were observed in both cases and controls.
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PMID:22 genes from chromosome 17q21: cloning, sequencing, and characterization of mutations in breast cancer families and tumors. 777 26

A cosmid mapped to human Chromosome (Chr) 17q21, c140c10, was found to contain a CpG island. We completed the sequence analysis of c140c10 because of two considerations: the cosmid contained an STS from the 17-beta-hydroxysteroid dehydrogenase gene (17-HSD), which was believed to be a neighbor of the breast cancer susceptibility gene, BRCA1; CpG islands are usually associated downstream and/or upstream of human genes. Computer-based exon trapping of the cosmid sequence revealed putative additional exons. With two of those exons used as a probe to screen human placental cDNA libraries, two cDNA isoforms for a novel gene, designated as ufHSD, were isolated. The amino acid sequence of the open reading frames of the cDNA showed no significant homology to any protein in the data base. However, it is possible that our cDNAs are from the gene for alpha-acetylglucosaminidase, which has recently been localized to the same region. Northern analyses show that the major isoform is expressed in all tissues tested, with the highest expression in blood leukocytes and lowest in brain. Finally, our study has shown that the 46.7-kb cosmid c140c10 encompasses loci for five genes and pseudo-genes: PsiPTP4A, ufHSD, 17-HSDI, 17-HSDII, and 22A1.
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PMID:Molecular dissection of a cosmid from a gene-rich region in 17q21 and characterization of a candidate gene for alpha-N-acetylglucosaminidase with two cDNA isoforms. 870 23