Abstract
CpG island methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. As yet, the number and identities of the genes that are inactivated in cancer cells has not been determined. In order to address this issue, we have performed a comprehensive isolation of CpG islands that are methylated in human lung adenocarcinomas. We have isolated approximately 200 CpG islands that are methylated in tumor DNA including those of known tumor-associated genes such as the HOXA5 gene. As the library contains the CpG islands of a number of known tumor suppressor genes it is highly likely that additional, previously unidentified tumor suppressor genes, will be present. On average, 1–2% of CpG islands were methylated specifically in tumors although this figure differed greatly between patients. This study provides an important resource in the search for genes inactivated in tumors and for the investigation of epigenetic dysregulation of gene expression by CpG island methylation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
02 October 2002
A Correction to this paper has been published: https://doi.org/10.1038/sj.onc.1205797
References
Ahuja N, Li Q, Mohan AL, Baylin SB, Issa JP . 1998 Cancer Res. 58: 5489–5494
Antequera F, Boyes J, Bird A . 1990 Cell 62: 503–514
Antequera F, Bird A . 1993 Proc. Natl. Acad. Sci. USA 90: 11995–11999
Baylin SB, Herman JG, Graff JR, Vertino PM, Issa J-P . 1998 Adv. Cancer Res. 72: 141–196
Bird AP . 1986 Nature 321: 209–213
Bird A . 2002 Genes Dev. 16: 6–21
Brock GJR, Charlton J, Bird A . 1999 Gene 240: 269–277
Costello JF, Früwald MC, Smiraglia DJ, Rush LJ, Robertson GP, Gao X, Wright FA, Feramisco JD, Peltomäki P, Lang JC et al . 2000 Nature Genet. 25: 132–138
Cross SH, Charlton JA, Nan X, Bird AP . 1994 Nature Genet. 6: 126–244
Dai Z, Lakshmanan RR, Zhu W-G, Smiraglia DJ, Rush LJ, Frühwald MC, Brena RM, Li B, Wright FA, Ross P Otterson GA, Plass C . 2001 Neoplasia 3: 314–323
Delgado S, Gómez M, Bird A, Antequera F . 1998 EMBO J. 17: 2426–2435
Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW, Molloy PL, Paul CL . 1992 Proc. Natl. Acad. Sci. USA 89: 1827–1831
Fuks F, Burgers WA, Brehm A, Hughes-Davis L, Kouzarides T . 2000 Nat. Genet. 24: 88–91
Hashimoto-Gotoh T, Tsujimura A, Kuriyama K, Matsuda S . 1993 Gene 137: 211–216
Hughes J, Ward CJ, Aspinwall R, Butler R, Harris PC . 1999 Hum. Mol. Genet. 8: 543–549
International Human Genome Sequencing Consortium. 2001 Nature 409: 860–921
Issa J-P, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB . 1994 Nature Genet. 7: 536–540
Larsen F, Gundersen G, Lopez R, Prydz H . 1992 Genomics 13: 1095–1107
Nguyen C, Liang G, Nguyen TT, Tsao-Wei D, Groshen S, Lübbert M, Zhou J-H, Benedict WF, Jones PA . 2001 J. Natl. Cancer Inst. 93: 1465–1472
Raman V, Martensen SA, Reisman D, Evron E, Odenwald WF, Jaffee E, Marks J, Sukumar S . 2000 Nature 405: 974–978
Robertson KD, Ait-Si-Ali S, Yokochi T, Wade P, Jones P, Wolffe AP . 2000 Nat. Genet. 25: 338–342
Rountree MR, Bachman KE, Baylin SB . 2000 Nat. Genet. 25: 269–277
Schmidt M, Migeon BR . 1990 Proc. Natl. Acad. Sci. USA 87: 3685–3689
Shiraishi M, Noguchi M, Shimosato Y, Sekiya T . 1989 Cancer Res. 49: 6474–6479
Shiraishi M, Lerman LS, Sekiya T . 1995 Proc. Natl. Acad. Sci. USA 92: 4229–4233
Shiraishi M, Oates AJ, Xu L, Hosoda F, Ohki M, Alitalo T, Lerman LS, Sekiya T . 1998 Nucleic Acids Res. 26: 5544–5550
Shiraishi M, Chuu YH, Sekiya T . 1999a Proc. Natl. Acad. Sci. USA 96: 2913–2918
Shiraishi M, Sekiguchi A, Chuu YH, Sekiya T . 1999b Biol. Chem. 380: 1127–1131
Shiraishi M, Lerman LS, Oates AJ, Xu L, Chuu YH, Sekiguchi A, Sekiya T . 2000 Gene Ther. Mol. Biol. 5: 35–42
Shiraishi M, Sekiguchi A, Oates AJ, Terry MJ, Miyamoto Y, Sekiya T . 2001 Proc. Japan Acad. 77: (B) 208–211
Shiraishi M, Oates AJ, Sekiya T . 2002 Biol. Chem in press
Short JM, Sorge JA . 1992 Meth. Enzymol. 216: 495–508
Tamaru H, Selker EU . 2001 Nature 414: 277–283
Tazi J, Bird A . 1990 Cell 60: 909–920
Thibonnier M, Graves MK, Wagner MS, Auzan C, Clauser E, Willard HF . 1996 Genomics 31: 372–334
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa J-P . 1999 Proc. Natl. Acad. Sci. USA 96: 8681–8686
Yoshiura K, Kanai Y, Ochiai A, Shimoyama Y, Sugimura T, Hirohashi S . 1995 Proc. Natl. Acad. Sci. USA 92: 7416–7419
Ugolini F, Charafe-Jauffret E, Bardou V-J, Geneix J, Adélaïde J, Labat-Moleur F, Penault-Llorca F, Longy M, Jacquemier J, Birnbaum D, Pébusque M-L . 2001 Oncogene 20: 5810–5817
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA et al . 2001 Science 291: 1304–1351
Acknowledgements
This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare of Japan, a Grant-in-Aid for Scientific Research on Priority Areas (C) ‘Medical Genome Science’ from the Ministry of Education, Science, Sports and Culture of Japan (to M Shiraishi), a Grant-in-Aid from the Ministry of Health and Welfare of Japan for the 2nd Term Comprehensive 10-Year Strategy for Cancer Control (to M Shiraishi and T Seikiya), a research Grant on Human Genome and Gene Therapy from the Ministry of Health and Welfare, Japan and a Grant from Takeda Science Foundation (to T Sekya). MJ Terry and YH Chuu were Research Fellows supported by the MIT Japan Program. AJ Oates was a Foreign Research Fellow of the Foundation for Promotion of Cancer Research, Japan.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shiraishi, M., Sekiguchi, A., Terry, M. et al. A comprehensive catalog of CpG islands methylated in human lung adenocarcinomas for the identification of tumor suppressor genes. Oncogene 21, 3804–3813 (2002). https://doi.org/10.1038/sj.onc.1205454
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205454
Keywords
This article is cited by
-
The novel TP53 3′-end methylation pattern associated with its expression would be a potential biomarker for breast cancer detection
Breast Cancer Research and Treatment (2020)
-
Epigenetically regulated PAX6 drives cancer cells toward a stem-like state via GLI-SOX2 signaling axis in lung adenocarcinoma
Oncogene (2018)
-
HOX gene clusters are hotspots of de novo methylation in CpG islands of human lung adenocarcinomas
Oncogene (2002)