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APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.

Publication ,  Journal Article
Arnold, CN; Goel, A; Niedzwiecki, D; Dowell, JM; Wasserman, L; Compton, C; Mayer, RJ; Bertagnolli, MM; Boland, CR
Published in: Cancer Biol Ther
October 2004

INTRODUCTION: Germ-line mutations of the APC gene are associated with familial adenomatous polyposis, and somatic mutations occur frequently in sporadic colorectal cancer. However, to abrogate APC function, both alleles must be inactivated. Recently, it has been demonstrated that epigenetic modification of the APC promoter influences APC silencing. Here we examined the influence of APC methylation on APC expression in tumors with and without LOH at the APC locus. MATERIAL AND METHODS: 137 sporadic colorectal cancer specimens were investigated for LOH at the 5q locus. The methylation status of the APC promoter was determined by methylation-specific PCR. APC expression was performed by immunohistochemistry. RESULTS: Expression was reduced or lost in 110 of 137 (80%) tumors and LOH at 5q was found in 13 of 132 (10%) tumors. There was no difference in 5q LOH between tumors with or without intact APC expression. Vice versa, there was no difference in the APC expression in tumors with 5q LOH. Aberrant APC promoter methylation was detected in 33 of 118 (28%) tumors investigated. Of the tumors with 5q LOH for which methylation data were available, 4 of 11 (36%) were methylated versus 28 of 105 (27%) of those without LOH. No difference in methylation was observed in tumors without 5q LOH and normal APC expression and those without 5q LOH and reduced or missing APC expression. Importantly, none of the tumors with 5q LOH and normal APC staining were aberrantly methylated, whereas 50% of the cancers with LOH at 5q and reduced or absent staining were hypermethylated. CONCLUSIONS: This report suggests that tumors with 5q LOH and reduced APC expression are more frequently hypermethylated at the APC promoter compared to those tumors with 5q LOH and normal APC expression. The association among APC promoter methylation status, 5q LOH, and reduced or lost APC expression suggests that de novo methylation plays an important role as a "second hit" in silencing APC expression in colorectal neoplasia.

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Published In

Cancer Biol Ther

DOI

ISSN

1538-4047

Publication Date

October 2004

Volume

3

Issue

10

Start / End Page

960 / 964

Location

United States

Related Subject Headings

  • Rectum
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Loss of Heterozygosity
  • Humans
  • Gene Silencing
  • Gene Expression Regulation, Neoplastic
  • DNA, Neoplasm
  • DNA Methylation
  • Colorectal Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Arnold, C. N., Goel, A., Niedzwiecki, D., Dowell, J. M., Wasserman, L., Compton, C., … Boland, C. R. (2004). APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther, 3(10), 960–964. https://doi.org/10.4161/cbt.3.10.1113
Arnold, Christian N., Ajay Goel, Donna Niedzwiecki, Jeannette M. Dowell, Linda Wasserman, Carolyn Compton, Robert J. Mayer, Monica M. Bertagnolli, and C Richard Boland. “APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.Cancer Biol Ther 3, no. 10 (October 2004): 960–64. https://doi.org/10.4161/cbt.3.10.1113.
Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, et al. APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther. 2004 Oct;3(10):960–4.
Arnold, Christian N., et al. “APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q.Cancer Biol Ther, vol. 3, no. 10, Oct. 2004, pp. 960–64. Pubmed, doi:10.4161/cbt.3.10.1113.
Arnold CN, Goel A, Niedzwiecki D, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM, Boland CR. APC promoter hypermethylation contributes to the loss of APC expression in colorectal cancers with allelic loss on 5q. Cancer Biol Ther. 2004 Oct;3(10):960–964.

Published In

Cancer Biol Ther

DOI

ISSN

1538-4047

Publication Date

October 2004

Volume

3

Issue

10

Start / End Page

960 / 964

Location

United States

Related Subject Headings

  • Rectum
  • Promoter Regions, Genetic
  • Oncology & Carcinogenesis
  • Loss of Heterozygosity
  • Humans
  • Gene Silencing
  • Gene Expression Regulation, Neoplastic
  • DNA, Neoplasm
  • DNA Methylation
  • Colorectal Neoplasms