The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
LINE‐1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer
Open accessAbstract
The CpG island methylator phenotype (CIMP) with widespread promoter CpG island methylation is a phenotype in colorectal cancer, associated with microsatellite instability (MSI) and BRAF mutation. Genome‐wide hypomethylation may also play an important role in genomic instability. However, the relation between global DNA methylation level and methylation in individual CpG islands remains uncertain. Utilizing 869 population‐based colorectal cancers, we measured long interspersed nucleotide element‐1 (LINE‐1) methylation level by Pyrosequencing, which correlates with global DNA methylation level. We quantified DNA methylation in 8 CIMP‐specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) by real‐time PCR (MethyLight technology). LINE‐1 methylation levels in tumors were approximately normally distributed (mean, 61.4%; median, 62.3%; standard deviation, 9.6%). Among the 869 tumors, 128 (15%) were classified as CIMP‐high (≥6/8 methylated promoters). The mean LINE‐1 methylation level was higher in CIMP‐high tumors (65.1%, p < 0.0001) than non‐CIMP‐high tumors (60.7%), and higher in MSI‐high tumors (64.7%, p < 0.0001) than non‐MSI‐high tumors (60.7%). When tumors were stratified by MSI/CIMP status, compared to non‐MSI‐high non‐CIMP‐high tumors (mean LINE‐1 methylation level, 60.4%), the mean LINE‐1 methylation level was higher in MSI‐high CIMP‐high (64.8%, p < 0.0001), MSI‐high non‐CIMP‐high (64.6%, p = 0.03) and non‐MSI‐high CIMP‐high tumors (66.1%, p = 0.0003). In addition, 18q loss of heterozygosity in non‐MSI‐high tumors was correlated with LINE‐1 hypomethylation (p = 0.004). In conclusion, both CIMP‐high and MSI‐high are inversely associated with LINE‐1 hypomethylation, suggesting that CIMP/MSI and genomic hypomethylation may represent different pathways to colorectal cancer. Our data also support a possible link between global hypomethylation and chromosomal instability. © 2008 Wiley‐Liss, Inc.
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CpG island methylator phenotype in colorectal cancer
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Induction of tumors in mice by genomic hypomethylation
Gaudet, F., Hodgson, J. G., Eden, A., Jackson-Grusby, L., Dausman, J., Gray, J. W., Leonhardt, H., & Jaenisch, R. (2003) · Science · doi:10.1126/science.1083558 · Cited by 1,499
MethyLight: a high-throughput assay to measure DNA methylation
Eads, C. A. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.8.e32 · Cited by 1,424
Jass, J. R. (2007) · Histopathology · doi:10.1111/j.1365-2559.2006.02549.x · Cited by 1,384
CpG island methylator phenotype in cancer
Issa, J.-P. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1507 · Cited by 1,098
A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
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Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of COX-2
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Self-citationAnalysis of repetitive element DNA methylation by MethyLight
Weisenberger, D. J. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki987 · Cited by 713
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Self-citationEpigenetics of colorectal cancer: biomarker and therapeutic potential
Jung, G., Hernández-Illán, E., Moreira, L., Balaguer, F., & Goel, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0230-y · Cited by 813
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Mima, K., Sukawa, Y., Nishihara, R., Qian, Z. R., Yamauchi, M., Inamura, K., Kim, S. A., Masuda, A., Nowak, J. A., Nosho, K., et al. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.1377 · Cited by 669
Self-citationNosho, K., Baba, Y., Tanaka, N., Shima, K., Hayashi, M., Meyerhardt, J. A., Giovannucci, E., Dranoff, G., Fuchs, C. S., & Ogino, S. (2010) · The Journal of Pathology · doi:10.1002/path.2774 · Cited by 502
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Metadata
- Authors
- Ogino, S., Kawasaki, T., Nosho, K., Ohnishi, M., Suemoto, Y., Kirkner, G. J., & Fuchs, C. S.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2008-04-09
- Volume
- 122
- Issue
- 12
- Pages
- 2767-2773
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2023473560
- Cited by
- 261
- References
- 53
- FWCI
- 18.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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