TY - JOUR
T1 - Aberrant CpG-island methylation has non-random and tumour-type-specific patterns
AU - Costello, Joseph F.
AU - Frühwald, Michael C.
AU - Smiraglia, Dominic J.
AU - Rush, Laura J.
AU - Robertson, Gavin P.
AU - Gao, Xin
AU - Wright, Fred A.
AU - Feramisco, Jamison D.
AU - Peltomäki, Päivi
AU - Lang, James C.
AU - Schuller, David E.
AU - Yu, Li
AU - Bloomfield, Clara D.
AU - Caligiuri, Michael A.
AU - Yates, Allan
AU - Nishikawa, Ryo
AU - Su Huang, H. J.
AU - Petrelli, Nicholas J.
AU - Zhang, Xueli
AU - O'Dorisio, M. Sue
AU - Held, William A.
AU - Cavenee, Webster K.
AU - Plass, Christoph
N1 - Funding Information:
We thank M.S. Berger, A. Asai, A. Tamura and N. Shitara for glioma samples; S. Edge and E. Repasky for help in obtaining primary breast tumour tissue; R. Lothe for testicular tumours, T. Weber and M.A. Rodriguez-Bigas for colon tumour samples; B. Chadwick and J. Weger for nucleotide sequencing; B. Yuan for the automated sequence analysis; J. Eisel, A. Morrow, J. Popovich and Y.-Z. Wu for technical assistance; C. DeSmet for helpful discussions; and Y. Hayashizaki and the late V. Chapman for advice and encouragement. We thank the Cooperative Human Tissue Network (CHTN) Midwestern Division and the CALGB Leukemia Tissue Bank for providing tissue samples. This work was supported in part by the National Cancer Institute grant P30 CA16058 and CA80912 (to C.P.), the Coleman Leukemia Research Foundation grant 3U10CA31946-17S3, the Children’s Hospital Research Foundation grant 216398, the Ladies Auxiliary of the Veterans of Foreign Wars grant 216498 and the Roswell Park Alliance Foundation. D.J.S. was supported by the Corixa Corporation and the T32 CA09338-20 Oncology Training Grant from the National Cancer Institute. M.C.F. was supported by a fellowship of the Dr. Mildred Scheel Stiftung für Krebsforschung/Deutsche Krebshilfe. J.F.C. was supported sequentially by the Basic Science Fellowship from the American Association for Cancer Research and by the Frances Goodrich and Albert Hackett Postdoctoral Fellowship from the American Brain Tumor Association.
PY - 2000/2
Y1 - 2000/2
N2 - 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.
AB - 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.
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U2 - 10.1038/72785
DO - 10.1038/72785
M3 - Article
C2 - 10655057
AN - SCOPUS:0343621494
VL - 24
SP - 132
EP - 138
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 2
ER -