|Title||CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer.|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||Cheng Y-W, Pincas H, Bacolod MD, Schemmann G, Giardina SF, Huang J, Barral S, Idrees K, Khan SA, Zeng Z, Rosenberg S, Notterman DA, Ott J, Paty P, Barany F|
|Journal||Clin Cancer Res|
|Date Published||2008 Oct 1|
|Keywords||Chromosomal Instability, Chromosome Aberrations, Colorectal Neoplasms, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Genome, Human, Humans, Male, Microsatellite Repeats, Mutation, Phenotype, Proto-Oncogene Proteins B-raf|
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.
|Alternate Journal||Clin. Cancer Res.|
|PubMed Central ID||PMC3268558|
|Grant List||P01 CA 65930 / CA / NCI NIH HHS / United States |
P01 CA065930-03 / CA / NCI NIH HHS / United States
P01 CA065930-04 / CA / NCI NIH HHS / United States
P01 CA065930-04S1 / CA / NCI NIH HHS / United States
P01 CA065930-04S2 / CA / NCI NIH HHS / United States
P01 CA065930-04S3 / CA / NCI NIH HHS / United States
P01 CA065930-05A2 / CA / NCI NIH HHS / United States
P01 CA065930-06 / CA / NCI NIH HHS / United States
P01 CA065930-07 / CA / NCI NIH HHS / United States
P01 CA065930-07S1 / CA / NCI NIH HHS / United States
P01 CA065930-08 / CA / NCI NIH HHS / United States
P01 CA065930-08S1 / CA / NCI NIH HHS / United States
R01 CA 81467 / CA / NCI NIH HHS / United States
R01 CA081467-02 / CA / NCI NIH HHS / United States
R01 CA081467-03 / CA / NCI NIH HHS / United States
T32 CA009501-19 / CA / NCI NIH HHS / United States
T32 CA009501-20 / CA / NCI NIH HHS / United States
Submitted by mam2155 on March 24, 2014 - 4:10pm