Association between CpG island methylation and microsatellite instability in colorectal cancer

Nita Ahuja, Avinash L. Mohan, Qing Li, Joshua M. Stolker, James G. Herman, Stanley R. Hamilton, Stephen B Baylin, Jean Pierre J Issa

Research output: Contribution to journalArticle

Abstract

De novo methylation of promoter region CpG islands has been increasingly associated with transcriptional inactivation of important genes in neoplasia. To study the potential mechanisms underlying aberrant methylation in cancer, we have determined the methylation patterns of selected genes in colorectal cancers with and without microsatellite instability (MI), which results from defects in one of several base mismatch repair genes. A total of 47 colorectal cancers were analyzed, of which 15 were MI+ (32%). We now report that both the frequency and the extent of de novo methylation are strikingly increased in MI+ cancers. Hypermethylation of the p16 gene was found in 60% of MI+ cancers, compared to only 22% in MI- cancers (P = 0.02). Similarly, hypermethylation of the thrombospondin-1 (TSP-1) gene, an angiogenesis inhibitor, was increased in MI+ cancers (27% versus 0%; P = 0.008). Extensive methylation of insulin-like growth factor II (IGF2) and hypermethylated in cancer-1 (HIC-1) genes was observed in 60 and 80% of MI+ cancers, respectively, as contrasted with 6 and 38% of MI- cancers (P = 0.0002 and 0.01, respectively). Furthermore, 60% of the MI+ cancers displayed the hypermethylation events at two or more loci in a concordant manner compared to only 9% of the MI- cancers (P <0.001). These results demonstrate a strong link between promoter hypermethylation and genetic instability due to deficient DNA repair.

Original languageEnglish (US)
Pages (from-to)3370-3374
Number of pages5
JournalCancer Research
Volume57
Issue number16
StatePublished - Aug 15 1997

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Microsatellite Instability
CpG Islands
Methylation
Colorectal Neoplasms
Neoplasms
Genetic Promoter Regions
DNA Repair-Deficiency Disorders
Genes
p16 Genes
Thrombospondin 1
DNA Mismatch Repair
Insulin-Like Growth Factor II
Angiogenesis Inhibitors
Neoplasm Genes
Gene Silencing

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ahuja, N., Mohan, A. L., Li, Q., Stolker, J. M., Herman, J. G., Hamilton, S. R., ... Issa, J. P. J. (1997). Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Research, 57(16), 3370-3374.

Association between CpG island methylation and microsatellite instability in colorectal cancer. / Ahuja, Nita; Mohan, Avinash L.; Li, Qing; Stolker, Joshua M.; Herman, James G.; Hamilton, Stanley R.; Baylin, Stephen B; Issa, Jean Pierre J.

In: Cancer Research, Vol. 57, No. 16, 15.08.1997, p. 3370-3374.

Research output: Contribution to journalArticle

Ahuja, N, Mohan, AL, Li, Q, Stolker, JM, Herman, JG, Hamilton, SR, Baylin, SB & Issa, JPJ 1997, 'Association between CpG island methylation and microsatellite instability in colorectal cancer', Cancer Research, vol. 57, no. 16, pp. 3370-3374.
Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR et al. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Research. 1997 Aug 15;57(16):3370-3374.
Ahuja, Nita ; Mohan, Avinash L. ; Li, Qing ; Stolker, Joshua M. ; Herman, James G. ; Hamilton, Stanley R. ; Baylin, Stephen B ; Issa, Jean Pierre J. / Association between CpG island methylation and microsatellite instability in colorectal cancer. In: Cancer Research. 1997 ; Vol. 57, No. 16. pp. 3370-3374.
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