Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 132-138 |
| Number of pages | 7 |
| Journal | Nature Genetics |
| Volume | 24 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2000 |
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All Science Journal Classification (ASJC) codes
- Genetics
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Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. / Costello, Joseph F.; Frühwald, Michael C.; Smiraglia, Dominic J.; Rush, Laura J.; Robertson, Gavin; 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. Sue; Held, William A.; Cavenee, Webster K.; Plass, Christoph.
In: Nature Genetics, Vol. 24, No. 2, 01.02.2000, p. 132-138.Research output: Contribution to journal › Article
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
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
PY - 2000/2/1
Y1 - 2000/2/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0343621494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0343621494&partnerID=8YFLogxK
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 -