CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer Journal Article
| Authors: | Cheng, Y. W.; Pincas, H.; Bacolod, M. D.; Schemmann, G.; Giardina, S. F.; Huang, J.; Barral, S.; Idrees, K.; Khan, S. A.; Zeng, Z.; Rosenberg, S.; Notterman, D. A.; Ott, J.; Paty, P.; Barany, F. |
| Article Title: | CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer |
| Abstract: | Purpose: Aberrant promoter methylation and genomic instability occur frequently during colorectal cancer development. CpG island methylator phenotype (CIMP) has been shown to associate with microsatellite instability, and BRAF mutation and is often found in the right-side colon. Nevertheless, the relative importance of CIMP and chromosomal instability (CIN) for tumorigenesis has yet to be thoroughly investigated in sporadic colorectal cancers. Experimental Design: We determined CIMP in 161 primary colorectal cancers and 66 matched normal mucosae using a quantitative bisulfite/PCR/ligase detection reaction (LDR)/Universal Array assay. The validity of CIMP was confirmed in a subset of 60 primary tumors using MethyLight assay and five independent markers. In parallel, CIN was analyzed in the same study cohort using Affymetrix 50K Human Mapping arrays. Results: The identified CIMP-positive cancers correlate with microsatellite instability (P = 0.075) and the BRAF mutation V600E (P = 0.00005). The array-based high-resolution analysis of chromosomal aberrations indicated that the degree of aneuploidy is spread over a wide spectrum among analyzed colorectal cancers. Whether CIN was defined by copy number variations in selected microsatellite loci (criterion 1) or considered as a continuous variable (criterion 2), CIMP-positive samples showed a strong correlation with low-degree chromosomal aberrations (P = 0.075 and P = 0.012, respectively). Similar correlations were observed when CIMP was determined by MethyLight assay (P = 0.001 and P = 0.013, respectively). Conclusion: CIMP-positive tumors generally possess lower chromosomal aberrations, which may only be revealed using a genome-wide approach. The significant difference in the degree of chromosomal aberrations between CIMP-positive and the remainder of samples suggests that epigenetic (CIMP) and genetic (CIN) abnormalities may arise from independent molecular mechanisms of tumor progression. ©2008 American Association for Cancer Research. |
| Keywords: | adolescent; adult; controlled study; human tissue; aged; unclassified drug; gene mutation; major clinical study; methylation; genetics; mutation; polymerase chain reaction; colorectal cancer; phenotype; pathology; microsatellite dna; dna methylation; carcinogenesis; colorectal neoplasms; gene expression regulation; chromosome aberration; gene expression regulation, neoplastic; cpg island; cpg islands; epigenesis, genetic; colorectal tumor; microsatellite instability; human genome; chromosomal instability; chromosome aberrations; genetic epigenesis; aneuploidy; b raf kinase; genome, human; proto-oncogene proteins b-raf; braf protein, human; microsatellite repeats; bisulfite |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-10-01 |
| Start Page: | 6005 |
| End Page: | 6013 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-0216 |
| PUBMED: | 18829479 |
| PROVIDER: | scopus |
| PMCID: | PMC3268558 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 23" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
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