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

Joseph F. Costello, Michael C. Frühwald, Dominic J. Smiraglia, Laura J. Rush, Gavin Robertson, Xin Gao, Fred A. Wright, Jamison D. Feramisco, Päivi Peltomäki, James C. Lang, David E. Schuller, Li Yu, Clara D. Bloomfield, Michael A. Caligiuri, Allan Yates, Ryo Nishikawa, H. J. Su Huang, Nicholas J. Petrelli, Xueli Zhang, M. Sue O'DorisioWilliam A. Held, Webster K. Cavenee, Christoph Plass

Research output: Contribution to journalArticle

1082 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)132-138
Number of pages7
JournalNature Genetics
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2000

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CpG Islands
Methylation
Neoplasms
Genome
Cultured Tumor Cells
Genes
Chromatin
Exons
Gene Expression

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Costello, J. F., Frühwald, M. C., Smiraglia, D. J., Rush, L. J., Robertson, G., Gao, X., ... Plass, C. (2000). Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nature Genetics, 24(2), 132-138. https://doi.org/10.1038/72785
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. / Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. In: Nature Genetics. 2000 ; Vol. 24, No. 2. pp. 132-138.
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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.",
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Costello, JF, Frühwald, MC, Smiraglia, DJ, Rush, LJ, Robertson, G, Gao, X, Wright, FA, Feramisco, JD, Peltomäki, P, Lang, JC, Schuller, DE, Yu, L, Bloomfield, CD, Caligiuri, MA, Yates, A, Nishikawa, R, Su Huang, HJ, Petrelli, NJ, Zhang, X, O'Dorisio, MS, Held, WA, Cavenee, WK & Plass, C 2000, 'Aberrant CpG-island methylation has non-random and tumour-type-specific patterns', Nature Genetics, vol. 24, no. 2, pp. 132-138. https://doi.org/10.1038/72785

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 journalArticle

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AU - Frühwald, Michael C.

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AU - Robertson, Gavin

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AU - Schuller, David E.

AU - Yu, Li

AU - Bloomfield, Clara D.

AU - Caligiuri, Michael A.

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AU - Nishikawa, Ryo

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AU - Petrelli, Nicholas J.

AU - Zhang, Xueli

AU - O'Dorisio, M. Sue

AU - Held, William A.

AU - Cavenee, Webster K.

AU - Plass, Christoph

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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.

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Costello JF, Frühwald MC, Smiraglia DJ, Rush LJ, Robertson G, Gao X et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nature Genetics. 2000 Feb 1;24(2):132-138. https://doi.org/10.1038/72785