High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer.

El‐Deiry, Wafik S.; Nelkin, Barry D.; Paul, C.; Yen, Ray Whay Chiu; Falco, Joseph; Hamilton, Stanley R.; Baylin, Stephen B.

doi:10.1073/pnas.88.8.3470

Cited by 279 publications

(188 citation statements)

References 42 publications

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“…DNA MTase expression has been assayed previously in lung, liver and colon tumour samples using a wide range of methods, including protein-based assays 21,22 and RNA-based assays 20,[22][23][24]37 and the results obtained have been variable. However, in this study we developed a standardised competitive RT-PCR assay which enabled accurate measurement of DNA MTase mRNA expression within and between samples.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Elevated levels of DNA MTase mRNA transcripts have been reported in colon cancer when compared to normal colon mucosa. Using non-quantitative reverse transcription RT-PCR assay, a 200-fold increase in DNA MTase mRNA levels was reported comparing colon cancers to normal mucosa, 20 whereas increases of 3.7-and 2.5-fold were found in later studies using quantitative RT-PCR 23 and RNAase protection assays, 24 respectively. DNA methylation patterns are known to be altered in a large number of genes in haematological malignancies.…”

Section: Introductionmentioning

confidence: 99%

“…18,19 Expression of DNA MTase has been extensively studied in colon cancer and it has been proposed that increased expression may be associated with altered DNA methylation patterns. 20 DNA MTase activity has been shown to increase progressively with advancing stages of both human colon and lung cancer. 21,22 Elevated levels of DNA MTase mRNA transcripts have been reported in colon cancer when compared to normal colon mucosa.…”

Section: Introductionmentioning

confidence: 99%

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Increased DNA methyltransferase expression in leukaemia

et al. 1998

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Aberrant DNA methylation has been observed consistently in many human tumours, in particular in the CpG islands of tumour suppressor genes, but the underlying mechanism of these changes remains unclear. To determine whether DNA methyltransferase expression is increased in leukaemia, we developed a standarised competitive RT-PCR assay to measure the level of DNA methyltransferase transcripts. Using this assay on bone marrow RNA samples from 12 patients with acute leukaemia, we observed a 4.4-fold mean increase in the level of DNA methyltransferase mRNA compared with normal bone marrow. These results support but do not prove the hypothesis that an increase in DNA methyltransferase activity is associated with malignant haematological diseases and may constitute a key step in carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Increased DNA methyltransferase expression in leukaemia

et al. 1998

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“…20 Elevated levels of DNMT-1 mRNA and DNMT activity have been observed in many cancer cells in vitro and tumors in vivo. 21,22 However, DNMT-1 mRNA is highly expressed in most fetal as well as adult tissues containing continuously renewing cell populations (e.g., liver), 20 showing a relationship between DNMT mRNA levels and the proliferative state of the tissue. Here, we show high expression of DNMT-1 in several tumor cell lines.…”

Section: Dnmt-1 Is Strongly Expressed In Cancer Cell Lines Mcf-7 Mdamentioning

confidence: 99%

A novel DNA methyltransferase I–derived peptide eluted from soluble HLA‐A*0201 induces peptide‐specific, tumor‐directed cytotoxic T cells

Berg

Barnea

Admon

et al. 2004

Intl Journal of Cancer

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Key words: soluble HLA; DNMT-1; cancer vaccine; tumor antigen; immunotherapyThe preferred approach for the elimination of tumor cells is to elicit a specific antitumor CTL response that will select tumor cells presenting the appropriate T-cell epitopes. 1-4 Human clinical trials for a variety of malignant diseases showed that T-cell therapy was effective and curative for some individuals. 5,6 A number of TAAs have been identified, mainly melanoma antigens, such as Melan-A and MART-1. Studies were initiated to vaccinate tumor patients against these antigens, and their ability to induce antitumor T-cell immunity has been shown in clinical studies. 7 Many of the recently identified antigens are nonmutated differentiation antigens overexpressed in tumors, e.g., a peptide derived from protein tyrosinase that was shown to successfully induce the attack and lysis of melanoma cells from cancer patients. 8 Several strategies have evolved to identify novel TAAs, e.g., cloning of epitopes recognized by CTLs 9 and SEREX technology, 10 where a patient's antibodies are used to identify tumor antigens from a cDNA expression library made from mRNA of tumor specimens.Conventionally, endogenous peptides have been eluted from affinity-purified HLA, such as HLA-A*0201, followed by analysis and sequencing using HPLC combined with tandem mass spectrometry. 11,12 HLA class I molecules are integral membrane glycoproteins; however, the presence of a soluble form of these molecules was demonstrated decades ago. 13,14 Similar to membrane-bound MHC, sMHC class I molecules bind peptides which are 8 -10 amino acids long, with a few exceptions having a length of 6, 11 and 12 amino acids. 15 Purification of MHC molecules is complicated due to their unavoidable contamination with cell debris and detergents after cell lysis. We recently identified HLA-restricted, tumor-specific antigens presented by the sMHC class I molecule by transfecting human tumor cell lines with truncated genes of HLA-A2. After purification of the secreted sHLA by affinity chromatography, peptides were eluted and sequenced. 15 Novel peptides unique to the sMHC variants were identified and screened for tumor-relevant precursor proteins. Detection of these peptides on sMHC indicates that these peptides are properly processed and displayed on transfected sMHC molecules similarly to those displayed on membrane-bound MHC molecules. Peptides recovered from sHLA molecules form similar patterns to those of membrane-bound HLA and include known MHC peptides. 15 Therefore, the repertoire of MHC peptides recovered from sMHC molecules is a good representation of the naturally processed and displayed peptides of transfected cells. Peptides detected this way should be presented at many copy numbers per cell and are likely to be bound with relatively high affinity to HLA.Use of sHLA as a source of peptides enabled us to identify large numbers of MHC peptides presented by human cancer cells and to screen these for peptides possibly derived from TAAs as candidates for tumor vaccination. 15 ...

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“…The American Cancer Society estimated that in 1995 more than 130 000 new cases of CRC would be diagnosed in the USA and that there would be 54 900 deaths from the disease (American Cancer Society, 1995). CRC onset and its progression has been studied extensively at the molecular (Bos et al, 1987;Forrester et al, 1987;Vogelstein et al, 1988;Burmer and Loeb, 1989;Delattre et al, 1989;Kern et al, 1989;Vogelstein et al, 1989;Fearon and Vogelstein, 1990;El-Deiry et al, 1991;Oudejans et al, 1991;Houlston et al, 1992;Laurent-Puig et al, 1992;Offerhaus et al, 1992;Sharrard et al, 1992;Bell et al, 1993;Finkelstein et al, 1993a and b;McLellan et al, 1993;Peltomaki et al, 1993;Urosevic et al, 1993;Breivik et al, 1994;Dix et al, 1994;Moerkerk et al, 1994;Morrin et al, 1994;Tanaka et al, 1994;Giaretti et al, 1995;Laird et al, 1995;Lewis et al, 1996;Span et al, 1996) and genetic (Woolf et al, 1958;Macklin et al, 1960;Houlston et al, 1992;Zhao and Le Marchand, 1992;Peltomaki et al, 1993;Goldgar et al, 1994;Lewis et al, 1996) levels and there is a commonly accepted model relating tumour grade according to Dukes' stage (Dukes, 1932) to specific DNA changes …”

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confidence: 99%

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system

Fox

England²,

White³

et al. 1998

Br J Cancer

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Summary A total of 301 colorectal carcinoma (CRC) archival samples were analysed using the amplification-refractory mutation system (ARMS). Each sample was examined to determine the mutation status of codons 12 and 13 of the K-ras oncogene. The results from direct DNA sequence analysis carried out on 30 of the samples differed from the ARMS result in almost 50% of the cases as a result of the relative excess of wild-type to mutated DNA sequences. To assess the validity of the ARMS data, the polymerase chain reaction (PCR) was used to generate an amplicon from K-ras exon from 23 of the samples. The PCR amplicons were cloned and sequenced, and the DNA sequence analysis of the cloned material was in agreement with the ARMS results in all but one case. This case represented a tumour that exhibited a five-nucleotide reversed inversion. The cloned sequence data confirm the sensitivity and specificity of the individual ARMS reactions and that it is possible in certain cases to detect additional, more complex, sequence variations.

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High expression of the DNA methyltransferase gene characterizes human neoplastic cells and progression stages of colon cancer.

Cited by 279 publications

References 42 publications

Increased DNA methyltransferase expression in leukaemia

Increased DNA methyltransferase expression in leukaemia

A novel DNA methyltransferase I–derived peptide eluted from soluble HLA‐A*0201 induces peptide‐specific, tumor‐directed cytotoxic T cells

The detection of K-ras mutations in colorectal cancer using the amplification-refractory mutation system

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