Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer

M. Esteller, A. Sparks, M. Toyota, M. Sanchez-Cespedes, G. Capella, M. A. Peinado, S. Gonzalez, G. Tarafa, David Sidransky, Stephen Meltzer, Stephen B Baylin, J. G. Herman

Research output: Contribution to journalArticle

Abstract

Germ-line mutations in the tumor suppressor gene APC are associated with hereditary familial adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal tumors. We now report that methylation in the promoter region of this gene constitutes an alternative mechanism for gene inactivation in colon and other tumors of the gastrointestinal tract. The APC promoter is hypermethylated in 18% of primary sporadic colorectal carcinomas (n = 108) and adenoma (n = 48), and neoplasia with APC methylation fails to express the APC transcript. Methylation affects only wild-type APC in 95% of cases and is not observed in tumors from FAP patients who have germ-line APC mutations. As with APC mutation, aberrant APC methylation occurs early in colorectal carcinogenesis. When other tumor types are analyzed (n = 208), methylation of the APC promoter is not restricted to the colon but is present in tumors originating elsewhere in the gastrointestinal tract but rarely in other tumors. Our data suggest that hypermethylation of APC provides an important mechanism for impairing APC function and further underscores the importance of the APC pathway in gastrointestinal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4366-4371
Number of pages6
JournalCancer Research
Volume60
Issue number16
StatePublished - Aug 15 2000

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Adenomatous Polyposis Coli
Methylation
Neoplasms
Germ-Line Mutation
Gastrointestinal Tract
Colorectal Neoplasms
Colon
Carcinogenesis
Mutation
Gene Silencing
Tumor Suppressor Genes
Genetic Promoter Regions
Adenoma
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Esteller, M., Sparks, A., Toyota, M., Sanchez-Cespedes, M., Capella, G., Peinado, M. A., ... Herman, J. G. (2000). Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Research, 60(16), 4366-4371.

Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. / Esteller, M.; Sparks, A.; Toyota, M.; Sanchez-Cespedes, M.; Capella, G.; Peinado, M. A.; Gonzalez, S.; Tarafa, G.; Sidransky, David; Meltzer, Stephen; Baylin, Stephen B; Herman, J. G.

In: Cancer Research, Vol. 60, No. 16, 15.08.2000, p. 4366-4371.

Research output: Contribution to journalArticle

Esteller, M, Sparks, A, Toyota, M, Sanchez-Cespedes, M, Capella, G, Peinado, MA, Gonzalez, S, Tarafa, G, Sidransky, D, Meltzer, S, Baylin, SB & Herman, JG 2000, 'Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer', Cancer Research, vol. 60, no. 16, pp. 4366-4371.
Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Research. 2000 Aug 15;60(16):4366-4371.
Esteller, M. ; Sparks, A. ; Toyota, M. ; Sanchez-Cespedes, M. ; Capella, G. ; Peinado, M. A. ; Gonzalez, S. ; Tarafa, G. ; Sidransky, David ; Meltzer, Stephen ; Baylin, Stephen B ; Herman, J. G. / Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. In: Cancer Research. 2000 ; Vol. 60, No. 16. pp. 4366-4371.
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