title: Toward a comprehensive and systematic methylome signature in colorectal cancers.
abstract: CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in colorectal cancer (CRC). This study aimed to define a methylome signature in CRC through a methylation microarray analysis and a compilation of promising CIMP markers from the literature. Illumina HumanMethylation27 (IHM27) array data was generated and analyzed based on statistical differences in methylation data (1st approach) or based on overall differences in methylation percentages using lower 95% CI (2nd approach). Pyrosequencing was performed for the validation of nine genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were hypermethylated in CRC but did not yet make it to the CIMP genes' list. Our 1st approach for array data analysis demonstrated the limitations in selecting genes for further validation, highlighting the need for the 2nd bioinformatics approach to adequately select genes with differential aberrant methylation. A more comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN, TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and TFPI2, was established. Array data are useful to categorize and cluster colonic lesions based on their global methylation profiles; however, its usefulness in identifying robust methylation markers is limited and rely on the data analysis method. We have identified 16 non-CIMP-panel genes for which we provide rationale for inclusion in a more comprehensive characterization of CIMP+ CRCs. The identification of a definitive list for methylome specific genes in CRC will contribute to better clinical management of CRC patients.
authors: Department of Medicine and Cancer Center; Department of Pathology; Howard University College of Medicine; Washington, D.C. USA.
authors: Hassan
authors: H
authors: Ashktorab
authors: Hamed
authors: H
authors: Rahi
authors: Daniel
authors: D
authors: Wansley
authors: Sudhir
authors: S
authors: Varma
authors: Babak
authors: B
authors: Shokrani
authors: Edward
authors: E
authors: Lee
authors: Mohammad
authors: M
authors: Daremipouran
authors: Adeyinka
authors: A
authors: Laiyemo
authors: Ajay
authors: A
authors: Goel
authors: John M
authors: JM
authors: Carethers
authors: Hassan
authors: H
authors: Brim
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D001741:Black or African American; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D059467:Transcriptome
keywords: African American; cancer; colon; methylation
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