Aberrant CpG-island methylation has non-random and tumour-type-specific patterns
Autor: | James C. Lang, Xueli Zhang, Gavin P. Robertson, David E. Schuller, William A. Held, Dominic J. Smiraglia, H.-J. Su Huang, Jamison D. Feramisco, Allan J. Yates, Clara D. Bloomfield, Webster K. Cavenee, Joseph F. Costello, Nicholas J. Petrelli, Li Yu, Xin Gao, Laura J. Rush, Fred A. Wright, M. S. O'Dorisio, Päivi Peltomäki, Christoph Plass, Michael C. Frühwald, Michael A. Caligiuri, Ryo Nishikawa |
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Rok vydání: | 2000 |
Předmět: |
Male
Bisulfite sequencing Restriction landmark genomic scanning Molecular Sequence Data Restriction Mapping Breast Neoplasms Biology Adenocarcinoma Epigenetics of physical exercise Neoplasms Genetics Humans Base Sequence Brain Neoplasms Genome Human Methylation DNA Methylation Carcinoma Lobular Differentially methylated regions Carcinoma Intraductal Noninfiltrating CpG site DNA methylation Colonic Neoplasms Illumina Methylation Assay Female Dinucleoside Phosphates |
Zdroj: | University of Helsinki |
ISSN: | 1061-4036 |
Popis: | 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. |
Databáze: | OpenAIRE |
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