Distinct hypermethylation patterns occur at altered chromosome loci in human lung and colon cancer

Michele Makos, Barry D. Nelkin, Michael I. Lerman, Farida Latif, Berton Zbar, Stephen B. Baylin

Research output: Contribution to journalArticlepeer-review

153 Scopus citations


Regional increases in DNA methylation occur in normally unmethylated cytosine-rich areas in neoplastic cells. These changes could potentially alter chromatin structure to inactivate gene transcription or generate DNA instability. We now show that, in human lung and colon cancer DNA, hypermethylation of such a region consistently occurs on chromosome 17p in an area that is frequently reduced to homozygosity in both tumor types. Over the progression stages of colon neoplasia, this methylation change increases in extent and precedes the allelic losses on 17p that are characteristic of colon carcinomas. We also show on chromosome 3p that regional hypermethylation may nonrandomly accompany chromosome changes in human neoplasia. Increased methylation is consistent in small-cell lung carcinoma DNA at two 3p loci that are constantly reduced to homozygosity in this tumor, but it is not seen in colon cancer DNA, in which these loci are infrequently structurally altered.

Original languageEnglish (US)
Pages (from-to)1929-1933
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - 1992


  • Allelic losses
  • CpG islands
  • Genetic instability

ASJC Scopus subject areas

  • General


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