DNA methylation and genetic instability in colorectal cancer cells

Lengauer, Christoph; Kinzler, Kenneth W.; Vogelstein, Bert

doi:10.1073/pnas.94.6.2545

Cited by 359 publications

(239 citation statements)

References 43 publications

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“…Gross changes include extensive changes in regional levels of methylation (both increased and decreased) (Laird and Jaenisch, 1994) as well as elevated levels of DNA methyltransferase (Melki et al, 1998;Lee et al, 1996). It has also recently been reported that colon cancer cell lines can be grouped into two classes which di er in their capacity to methylate introduced retroviral genomes (Lengauer et al, 1997) this has been interpreted to indicate that while defects in mismatch repair systems are critical early events leading to cancer development, alterations to the regulation of DNA methylation may provide an alternate route.…”

Section: Discussionmentioning

confidence: 99%

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

et al. 1999

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Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the p-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not con®ned to speci®c CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no e ect on gene expression.

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Section: Discussionmentioning

confidence: 99%

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

et al. 1999

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“…Pathways leading to CIN and MIN phenotypes are not mutually exclusive and they have common end points, such as LOH. 33 Likewise, two genetically distinct categories of neuroblastoma can be identified: those with gross abnormalities in chromosome number characterized by hyperdiploidy (primarily stage 4s, and most local-regional tumors) and those that are characteristically diploid but frequently have regional amplifications and deletions (primarily stage 4 tumors). Each of these groups has distinct clinical behavior with significant differences in survival rates.…”

Section: Discussionmentioning

confidence: 99%

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

Mora

Cheung

Kushner

et al. 2000

The Journal of Molecular Diagnostics

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“…[12][13][14] Global hypomethylation of cytosine residues in the DNA has been reported in a diverse group of tumors. [15][16][17] Long interspersed nucleotide elements (LINE) are 6-8 kb long, GC-poor sequences encoding an RNA-binding protein and a reverse transcriptase/endonuclease making up 15% of human genome with half a million copies, and LINE-1 are the most abundant. 18,19 Alu-repetitive elements are shorter, B300 bp in length, GC-rich, derived from 7SL RNA, and make up 10% of human genome with B1.4 million copies.…”

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confidence: 99%

Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors)

et al. 2007

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Neuroendocrine tumors including carcinoid tumors and pancreatic endocrine tumors are uncommon, and the genetic alterations in these indolent tumors are not well characterized. We studied global hypomethylation by analyzing long interspersed nucleotide elements (LINE)-1 and Alu methylation using pyrosequencing in 35 neuroendocrine tumors and corresponding normal tissue. The tumor samples were less methylated than normal tissue at LINE-1 (P ¼ 0.04) and Alu (P ¼ 0.001). The mean relative tumor hypomethylation (difference in methylation between normal tissue and in tumor) was 11.5710.0 for LINE-1 and 5.876.4 for Alu, and were correlated with each other (correlation coefficient 0.6, P ¼ 0.001). Relative tumor hypomethylation of LINE-1 was higher in ileal carcinoid tumors than in non-ileal carcinoid tumors and pancreatic endocrine tumors (P ¼ 0.047), and tumors with lymph node metastasis (P ¼ 0.02), chromosome 18 loss (P ¼ 0.001) and RAS-association domain family 1, isoform A gene methylation (P ¼ 0.02). Alu methylation in tumors was inversely correlated with methylation of O 6 -methyl-guanine methyltransferase gene (P ¼ 0.02). Our study shows that hypomethylation is more common in carcinoid tumors than in pancreatic endocrine tumors and is associated with clinicopathologic features, and genetic and epigenetic alterations in these tumors, including lymph node metastasis.

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DNA methylation and genetic instability in colorectal cancer cells

Cited by 359 publications

References 43 publications

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

Detailed methylation analysis of the glutathione S-transferase π (GSTP1) gene in prostate cancer

Clinical Categories of Neuroblastoma Are Associated with Different Patterns of Loss of Heterozygosity on Chromosome Arm 1p

Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors)

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