Cancer Research Meeting Calendar  Genetics and Biology of Brain Cancer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Cancer Research 67, 11335, December 1, 2007. doi: 10.1158/0008-5472.CAN-07-1502
© 2007 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shen, L.
Right arrow Articles by Issa, J.-P. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, L.
Right arrow Articles by Issa, J.-P. J.

Experimental Therapeutics, Molecular Targets, and Chemical Biology

Drug Sensitivity Prediction by CpG Island Methylation Profile in the NCI-60 Cancer Cell Line Panel

Lanlan Shen1, Yutaka Kondo2, Saira Ahmed1, Yanis Boumber1, Kazuo Konishi1, Yi Guo1, Xinli Chen1, Jill N. Vilaythong1 and Jean-Pierre J. Issa1

1 Department of Leukemia, the University of Texas M. D. Anderson Cancer Center, Houston, Texas and 2 Aichi Cancer Center, Division of Molecular Oncology, Nagoya, Japan

Requests for reprints: Lanlan Shen, Department of Leukemia, M. D. Anderson Cancer Center, Unit 428, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-9854; Fax: 713-792-2638; E-mail: lshen{at}mdanderson.org.

Aberrant promoter hypermethylation and associated gene silencing are epigenetic hallmarks of tumorigenesis. It has been suggested that aberrant DNA methylation can affect the sensitivity of cancers to antineoplastic agents by altering expression of genes critical to drug response. To study this issue, we used bisulfite PCR to assess DNA methylation of 32 promoter-associated CpG islands in human cancer cell lines from the National Cancer Institute (NCI) drug-screening panel (NCI-60 panel). The frequency of aberrant hypermethylation of these islands ranged from 2% to 81% in NCI-60 cancer cells, and provided a database that can be analyzed for the sensitivity to {approx}30,000 drugs tested in this panel. By correlating drug activity with DNA methylation, we identified a list of methylation markers that predict sensitivity to chemotherapeutic drugs. Among them, hypermethylation of the p53 homologue p73 and associated gene silencing was strongly correlated with sensitivity to alkylating agents. We used small interfering RNA to down-regulate p73 expression in multiple cell lines, including the resistant cell lines TK10 (renal cancer) and SKMEL28 (melanoma). Down-regulating p73 substantially increased sensitivity to commonly used alkylating agents, including cisplatin, indicating that epigenetic silencing of p73 directly modulates drug sensitivity. Our results confirm that epigenetic profiles are useful in identifying molecular mediators for cancer drug sensitivity (pharmaco-epigenomics). [Cancer Res 2007;67(23):11335–43]




This article has been cited by other articles:


Home page
Nucleic Acids ResHome page
B. J. Evison, R. A. Bilardi, F. C. K. Chiu, G. Pezzoni, D. R. Phillips, and S. M. Cutts
CpG methylation potentiates pixantrone and doxorubicin-induced DNA damage and is a marker of drug sensitivity
Nucleic Acids Res., October 1, 2009; 37(19): 6355 - 6370.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. Nojima, R. Maruyama, H. Yasui, H. Suzuki, Y. Maruyama, I. Tarasawa, Y. Sasaki, H. Asaoku, H. Sakai, T. Hayashi, et al.
Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma
Clin. Cancer Res., July 1, 2009; 15(13): 4356 - 4364.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
M. T. McCabe, J. C. Brandes, and P. M. Vertino
Cancer DNA Methylation: Molecular Mechanisms and Clinical Implications
Clin. Cancer Res., June 15, 2009; 15(12): 3927 - 3937.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2007 by the American Association for Cancer Research.