Polymerase δ variants in RER colorectal tumours

Costa, Luís Teixeira da; Liu, Bo; El‐Deiry, Wafik S.; Hamilton, Stanley R.; Kinzler, Kenneth W.; Vogelstein, Bert; Markowitz, Sanford D.; Willson, James K.V.; Chapelle, Albert de la; Downey, Kathleen M.; So, Antero G.

doi:10.1038/ng0195-10

Cited by 117 publications

(72 citation statements)

References 13 publications

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“…However, cell lines deficient in GTBP and another mismatch repair enzyme, DNA polymerase ␦, do not and so functional loss of these proteins would not necessarily be detected by this study. 14,49 The association of LOH of DNA mismatch repair genes loci and microsatellite instability is unusual but has been previously reported in two circumstances. Microsatellite instability and LOH at the hMLH1 locus on 3p21-findings similar to this study-has been reported in non-small cell lung carcinomas, 50 while Parsons et al 51 described microsatellite instability in lymphocytes from some but not all patients with hereditary nonpolyposis colon cancer caused by mutations of DNA mismatch repair genes.…”

Section: Discussionmentioning

confidence: 97%

Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis

et al. 1998

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DNA mismatch repair is an important mechanism involved in maintaining the fidelity of genomic DNA. Defective DNA mismatch repair is implicated in a variety of gastrointestinal and other tumors; however, its role in hepatocellular carcinoma (HCC) has not been assessed. Formalin-fixed, paraffin-embedded archival pathology tissues from 46 primary liver tumors were studied by microdissection and microsatellite analysis of extracted DNA to assess the degree of microsatellite instability, a marker of defective mismatch repair, and to determine the extent and timing of allelic loss of two DNA mismatch repair genes, human Mut S homologue-2 (hMSH2) and human Mut L homologue-1 (hMLH1), and the tumor suppressor genes adenomatous polyposis coli gene (APC), p53, and DPC4. Microsatellite instability was detected in 16 of the tumors (34.8%). Loss of heterozygosity at microsatellites linked to the DNA mismatch repair genes, hMSH2 and/or hMLH1, was found in 9 cases (19.6%), usually in association with microsatellite instability. Importantly, the pattern of allelic loss was uniform in 8 of these 9 tumors, suggesting that clonal loss had occurred. Moreover, loss at these loci also occurred in nonmalignant tissue adjacent to 4 of these tumors, where it was associated with marked allelic heterogeneity. There was relatively infrequent loss of APC, p53, or DPC4 loci that appeared unrelated to loss of hMSH2 or hMLH1 gene loci. Loss of heterozygosity at hMSH2 and/or hMLH1 gene loci, and the associated microsatellite instability in premalignant hepatic tissues suggests a possible causal role in hepatic carcinogenesis in a subset of hepatomas. (HEPATOLOGY 1998;28:90-97.)

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Section: Discussionmentioning

confidence: 97%

Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis

et al. 1998

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“…It seems clear that HNPCC families, sporadic tumors, and tumor cell lines that are associated with mismatch repair defects or that exhibit microsatellite instability exist where it has not yet been possible to demonstrate defects in known mismatch repair genes (da Costa et al 1995;Katabuchi et al 1995;Liu et al 1995Liu et al , 1996Papadopoulos et al 1995;Wijnen et al 1995Wijnen et al , 1996. This observation has provided additional interest in the identification of other components of eukaryotic mismatch repair.…”

Section: Other Components Required For Mismatch Repairmentioning

confidence: 99%

Biochemistry and genetics of eukaryotic mismatch repair.

Kolodner¹

1996

Genes Dev.

554

415

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“…Sense (s) and antisense (a) primers for ampli®cation of aE-catenin cDNA (s1, s2, s3, a1, a2 and a3) were previously published by Oda et al, 1993 and purchased from Gibco. Previously described primers for the ampli®cation of DNA polymerase d (da Costa et al, 1995) and HMSH6 (Papadopoulos et al, 1995) were used. DNA-free RNA was reverse transcribed and ampli®ed with AmpliTaq Gold TM (Perkin Elmer) in a Programmable Thermal Controller-100 (MJ Research, Watertown, MA, USA).…”

Section: Rt ± Pcrmentioning

confidence: 99%

“…Sequencing primers for a-catenin were the same as for the generation of the PCR-products. Primers for DNA polymerase d and HMSH6 were generated on the basis of the published sequences (da Costa et al, 1995;Papadopoulos et al, 1995). Sequences were analysed by the Lasergene software (DNASTAR, Madison, WI, USA).…”

Section: Protein Truncation Test (Ptt)mentioning

confidence: 99%

The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

Vermeulen

Nollet

Teugels³

et al. 1999

Oncogene

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The acquisition of invasiveness is a crucial step in the malignant progression of cancer. In cancers of the colon and of other organs the E-cadherin/catenin complex, which is implicated in homotypic cell-cell adhesion as well as in signal transduction, serves as a powerful inhibitor of invasion. We show here that one allele of the aE-catenin (CTNNA1) gene is mutated in the human colon cancer cell family HCT-8, which is identical to HCT-15, DLD-1 and HRT-18. Genetic instability, due to mutations in the HMSH6 (also called GTBP) mismatch repair gene, results in the spontaneous occurrence of invasive variants, all carrying either a mutation or exon skipping in the second aE-catenin allele. The aE-catenin gene is therefore, an invasionsuppressor gene in accordance with the two-hit model of Knudsen for tumour-suppressor genes.

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Polymerase δ variants in RER colorectal tumours

Cited by 117 publications

References 13 publications

Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis

Microsatellite instability and loss of heterozygosity at DNA mismatch repair gene loci occurs during hepatic carcinogenesis

Biochemistry and genetics of eukaryotic mismatch repair.

The αE-catenin gene (CTNNA1) acts as an invasion-suppressor gene in human colon cancer cells

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