Aberrant CpG-island methylation has non-random and tumour-type-specific patterns

• Published in: Nature genetics Vol. 24; no. 2; pp. 132 - 138
• Main Authors: Costello, Joseph F, Plass, Christoph, Frühwald, Michael C, Smiraglia, Dominic J, Rush, Laura J, Robertson, Gavin P, Gao, Xin, Wright, Fred A, Feramisco, Jamison D, Peltomäki, Päivi, Lang, James C, Schuller, David E, Yu, Li, Bloomfield, Clara D, Caligiuri, Michael A, Yates, Allan, Nishikawa, Ryo, Su Huang, H.-J, Petrelli, Nicholas J, Zhang, Xueli, O 'Dorisio, M. S, Held, William A, Cavenee, Webster K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.02.2000
• Subjects: Adenocarcinoma - genetics; Base Sequence; Biological and medical sciences; Brain Neoplasms - genetics; Breast Neoplasms - genetics; Cancer; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Lobular - genetics; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Classical genetics, quantitative genetics, hybrids; Cloning; Colonic Neoplasms - genetics; Dinucleoside Phosphates - analysis; Dinucleoside Phosphates - genetics; DNA Methylation; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Genomes; Human; Humans; Islands; Male; Methylation; Molecular and cellular biology; Molecular Sequence Data; Neoplasms - genetics; Oncogenes; Oncology; Restriction Mapping; Tumors; United States > US; Ohio; California; Human; Tumor; Methylation; Carcinogenesis; DNA
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/72785

CpG islands frequently contain gene promoters or exons and are usually unmethylated in normal cells. Methylation of CpG islands is associated with delayed replication, condensed chromatin and inhibition of transcription initiation. The investigation of aberrant CpG-island methylation in human cancer has primarily taken a candidate gene approach, and has focused on less than 15 of the estimated 45,000 CpG islands in the genome. Here we report a global analysis of the methylation status of 1,184 unselected CpG islands in each of 98 primary human tumours using restriction landmark genomic scanning (RLGS). We estimate that an average of 600 CpG islands (range of 0 to 4,500) of the 45,000 in the genome were aberrantly methylated in the tumours, including early stage tumours. We identified patterns of CpG-island methylation that were shared within each tumour type, together with patterns and targets that displayed distinct tumour-type specificity. The expression of many of these genes was reactivated by experimental demethylation in cultured tumour cells. Thus, the methylation of particular subsets of CpG islands may have consequences for specific tumour types.