CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Export

@article{citeulike:3371869, 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.}, author = {Cheng, Y. W. and Pincas, H. and Bacolod, M. D. and Schemmann, G. and Giardina, S. F. and Huang, J. and Barral, S. and Idrees, K. and Khan, S. A. and Zeng, Z. and Rosenberg, S. and Notterman, D. A. and Ott, J. and Paty, P. and Barany, F.}, citeulike-article-id = {3371869}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-08-0216}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18829479}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18829479}, doi = {10.1158/1078-0432.CCR-08-0216}, issn = {1078-0432}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, keywords = {colon\_cancer, copy-number, methylation}, month = {October}, number = {19}, pages = {6005--6013}, posted-at = {2009-01-10 16:40:23}, priority = {2}, title = {CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer.}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-08-0216}, volume = {14}, year = {2008} }

TY - JOUR ID - citeulike:3371869 L3 - citeulike-article-id:3371869 N2 - 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. IS - 19 JF - Clinical cancer research : an official journal of the American Association for Cancer Research SN - 1078-0432 EP - 6013 TI - CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. VL - 14 SP - 6005 KW - colon_cancer KW - copy-number KW - methylation AU - Cheng, YW AU - Pincas, H AU - Bacolod, MD AU - Schemmann, G AU - Giardina, SF AU - Huang, J AU - Barral, S AU - Idrees, K AU - Khan, SA AU - Zeng, Z AU - Rosenberg, S AU - Notterman, DA AU - Ott, J AU - Paty, P AU - Barany, F PY - 2008/10/01/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-08-0216 ER -