Emerging pathways in colorectal-cancer development

Andrew M.M. Haydon, Jeremy R. Jass

Research output: Contribution to journalReview ArticleResearchpeer-review

125 Citations (Scopus)


The past decade has seen the emergence of new pathways in the development of colorectal cancer. There is now clear evidence that subsets of these tumours do not show chromosomal instability and do not follow the suppressor pathway. Instead, about 15% of colorectal cancers are characterised by microsatellite instability (MSI). This feature arises through defective DNA mismatch repair, which is related either to a germline mutation (as in hereditary non-polyposis colorectal carcinoma) or to failure to express a mismatch-repair gene. CpG-island methylation has been linked to sporadic cancers with a high frequency of MSI. This type of methylation leads to loss of gene expression when it occurs in the promoter region of a gene. Tumours may have high or low type C (cancer-related) CpG-island methylation. When methylation affects hMLH1 (mismatch repair gene), the resultant cancer has high MSI.

Original languageEnglish
Pages (from-to)83-88
Number of pages6
JournalThe Lancet Oncology
Issue number2
Publication statusPublished - 1 Jan 2002

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