Research Topics
Genomes and Genes | Peter A JonesSummaryAffiliation: University of Southern California Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Cell division is required for de novo methylation of CpG islands in bladder cancer cellsMihaela Velicescu
Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90089-9181, USA
Cancer Res 62:2378-84. 2002..Our results suggest that cell division is required for de novo methylation of CpG islands and that DNMT3a may play a role in methylating CpG poor regions or repetitive DNA elements outside of the S phase of the cell cycle...
The role of DNA methylation in mammalian epigeneticsP A Jones
USC Norris Comprehensive Cancer Center, Departments of Biochemistry and Molecular Biology, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, CA 90089 9181, USA
Science 293:1068-70. 2001....
The fundamental role of epigenetic events in cancerPeter A Jones
USC Norris Comprehensive Cancer Center, Department of Urology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, California 90089 9181, USA
Nat Rev Genet 3:415-28. 2002..In this review, we discuss these epigenetic events and the molecular alterations that might cause them and/or underlie altered gene expression in cancer...
DNA methylation and cancerPeter A Jones
USC Norris Comprehensive Cancer Center, Department of Urology, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, California, CA 90089 9181
Oncogene 21:5358-60. 2002..Understanding these processes is fundamental to understanding what goes awry during the process of aging and carcinogenesis where DNA methylation patterns become substantially altered and contribute to the malignant phenotype...
A blueprint for a Human Epigenome Project: the AACR Human Epigenome WorkshopPeter A Jones
University of Southern California Norris Comprehensive Cancer Center, Los Angeles, 90089, USA
Cancer Res 65:11241-6. 2005..A timely workshop of leading experts, convened by the American Association for Cancer Research (AACR), confirmed that the technology is at hand to begin defining human epigenomes at high resolution...
An epigenetic approach for finding tumor suppressorsPeter A Jones
Department of Urology, USC/Norris Comprehensive Cancer Center, Los Angeles, CA 90089-9181, USA
Cell Cycle 2:25-6. 2003
Epigenetics in carcinogenesis and cancer preventionPeter A Jones
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089 9181, USA
Ann N Y Acad Sci 983:213-9. 2003....
Overview of cancer epigeneticsPeter A Jones
Department of Urology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90089 9181, USA
Semin Hematol 42:S3-8. 2005..In addition, changed patterns of methylation can be detected with a high degree of sensitivity thus providing clinicians with prognostic information...
H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genesTheresa K Kelly
Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Mol Cell 39:901-11. 2010..These key changes provide a potential mechanism for rapid silencing and reactivation of genes during the cell cycle...
DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylationTina Branscombe Miranda
Department of Urology, USC Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Mol Cancer Ther 8:1579-88. 2009..This suggests that there is a homeostatic mechanism that returns the histone modifications to their "ground state" after DZNep treatment. Our data show the strong need for further development of histone methylation inhibitors...
Preferential response of cancer cells to zebularineJonathan C Cheng
USC/Norris Comprehensive Cancer Center, Departments of Urology, Biochemistry, and Molecular Biology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Cancer Cell 6:151-8. 2004..Our results demonstrate that zebularine can be selective toward cancer cells and may hold clinical promise as an anticancer therapy...
DNA methylation screening identifies driver epigenetic events of cancer cell survivalDaniel D De Carvalho
Department of Urology, Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9181, USA
Cancer Cell 21:655-67. 2012..We further showed experimentally that these genes must be silenced by DNA methylation for cancer cell survival, suggesting these are key epigenetic events associated with tumorigenesis...
Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG islandJoy C Lin
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Cancer Cell 12:432-44. 2007..Activation of the promoter by demethylation with 5-aza-2'-deoxycytidine involves nucleosome eviction. Epigenetic silencing of tumor suppressor genes may involve heritable changes in nucleosome occupancy enabled by cytosine methylation...
Role of the DNA methyltransferase variant DNMT3b3 in DNA methylationDaniel J Weisenberger
Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Los Angeles, CA 90089-9181, USA
Mol Cancer Res 2:62-72. 2004..Methylation analyses of immunodeficiency, chromosomal instabilities, and facial abnormalities cells revealed that an Alu repeat sequence was highly methylated, suggesting that Alu sequences are not DNMT3b targets...
Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNAShinWu Jeong
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, NOR 8302L, 9181, Los Angeles, CA 90089 9181, USA
Mol Cell Biol 29:5366-76. 2009..These data suggest that inheritance of DNA methylation requires cues from the chromatin component in addition to hemimethylation...
Dynamic nucleosome-depleted regions at androgen receptor enhancers in the absence of ligand in prostate cancer cellsClaudia Andreu-Vieyra
Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA
Mol Cell Biol 31:4648-62. 2011..quot; This allows the recruitment of histone modifiers, chromatin remodelers, and ultimately gene activation. The "receptive" state described here could help explain AR signaling activation under very low ligand concentrations...
Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritanceShikhar Sharma
Department of Urology, Biochemistry, and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 7:e1001286. 2011....
Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell lineEinav Nili Gal-Yam
Department of Urology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9181, USA
Proc Natl Acad Sci U S A 105:12979-84. 2008....
Inhibition of histone deacetylation does not block resilencing of p16 after 5-aza-2'-deoxycytidine treatmentGerda Egger
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Cancer Res 67:346-53. 2007..Altogether, our data provide new insights into the mechanism of epigenetic drugs and have important implications for epigenetic therapy...
Long-term epigenetic therapy with oral zebularine has minimal side effects and prevents intestinal tumors in miceChristine B Yoo
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033 9181, USA
Cancer Prev Res (Phila) 1:233-40. 2008..Importantly, prolonged treatment of mice with epigenetic drugs resulted in only minor developmental and histologic changes...
Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genomeGangning Liang
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, CA 90089 9181
Proc Natl Acad Sci U S A 101:7357-62. 2004..Common models depicting widespread histone acetylation and K4 methylation throughout the transcribed unit do not therefore apply to the majority of human genes...
The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2Jeffrey M Friedman
Department of Urology, Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Cancer Res 69:2623-9. 2009..We conclude that miR-101 may be a potent tumor suppressor by altering global chromatin structure through repression of EZH2...
Gene reactivation by 5-aza-2'-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regionsXiaojing Yang
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 8:e1002604. 2012..Furthermore, we elucidate that chromatin remodeling translates the demethylation ability of DNMT inhibitors to their downstream efficacies, suggesting future therapeutic implications for chromatin remodelers...
DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoterHan Han
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA
Hum Mol Genet 20:4299-310. 2011....
Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancerErika M Wolff
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 6:e1000917. 2010..These data show that, in addition to contributing to chromosomal instability, hypomethylation of LINE-1s can alter the functional transcriptome and plays a role not only in human disease but also in disease predisposition...
Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidineJody C Chuang
USC/Norris Comprehensive Cancer Center, Department of Urology, Biochemistry, and Molecular Biology, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Mol Cancer Ther 4:1515-20. 2005..We found that 5-Aza-CdR is far more effective in DNA methylation inhibition as well as in reactivating genes, compared with non-nucleoside inhibitors...
Unique DNA methylation patterns distinguish noninvasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissueErika M Wolff
Department of Urology, USC Epigenome Center, and Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089, USA
Cancer Res 70:8169-78. 2010..In addition, an epithelium-wide epigenetic defect in bladders with cancer might contribute to a loss of epithelial integrity and create a permissible environment for tumors to arise...
Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cellsYoshimasa Saito
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA
Cancer Cell 9:435-43. 2006..These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors...
Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survivalGerda Egger
Norris Comprehensive Cancer Center, Departments of Urology and Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Proc Natl Acad Sci U S A 103:14080-5. 2006..Our data suggest that DNMT1 might be essential for maintenance of DNA methylation, proliferation, and survival of cancer cells...
S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growthJody C Chuang
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Mol Cancer Ther 9:1443-50. 2010..We also show that S110 is effective by both i.p. and s.c. deliveries. S110 therefore is a promising new agent that acts similarly to 5-Aza-CdR and has better stability and less toxicity...
Polycomb-repressed genes have permissive enhancers that initiate reprogrammingPhillippa C Taberlay
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Cell 147:1283-94. 2011..Genome-wide, a high percentage of Polycomb targets are associated with putative enhancers in permissive states, suggesting that they may provide a widespread avenue for the initiation of cell-fate reprogramming...
Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinomaMartin G Friedrich
Department of Urology, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089 9176, USA
Eur J Cancer 41:2769-78. 2005..We identified one gene (TIMP-3) where methylation was associated with a more favourable outcome. Our data strongly support the usefulness of gene methylation as a prognostic marker in patients with non-muscle invasive bladder cancer...
Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2'-deoxycytidineCarvell T Nguyen
Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center and Hospital, University of Southern California, Keck School of Medicine, Los Angeles, California 90089, USA
Cancer Res 62:6456-61. 2002..In addition, 5-Aza-CdR increased acetylation and H3-K4 methylation at the unmethylated p14 promoter, suggesting it can induce chromatin remodeling independently of its effects on cytosine methylation...
OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genesJueng Soo You
Department of Urology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Proc Natl Acad Sci U S A 108:14497-502. 2011..These data show the central role of the NDRs, established by OCT4, in ensuring the autoregulatory loop of pluripotency and, furthermore, that de novo methylation follows the loss of NDRs and stabilizes the suppressed state...
Delivery of 5-aza-2'-deoxycytidine to cells using oligodeoxynucleotidesChristine B Yoo
Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
Cancer Res 67:6400-8. 2007..This approach may pave the way for more stable and potent inhibitors of DNA methylation as well as provide means for improving existing therapeutics...
Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patientsMartin G Friedrich
Departments of Urology, Clinical Pathology, and Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089-9176, USA
Clin Cancer Res 10:7457-65. 2004..Our results also indicate that some methylation markers, such as those in regions of RASSF1A and TNFRSF25, might be of limited use for detection because they are also methylated in normal bladder tissues...
Constitutive nucleosome depletion and ordered factor assembly at the GRP78 promoter revealed by single molecule footprintingEinav Nili Gal-Yam
Department of Urology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America
PLoS Genet 2:e160. 2006..Studying the positioning of nucleosomes and transcription factors at the single promoter level provides a powerful tool to gain novel insights into the transcriptional process in eukaryotes...
Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2'-deoxyzebularineChristine B Yoo
Department of Biochemistry, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
J Med Chem 51:7593-601. 2008..Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma cells...
Identification of DNA methylation differences during tumorigenesis by methylation-sensitive arbitrarily primed polymerase chain reactionGangning Liang
Department of Biochemistry and Molecular Biology, Urologic Cancer Research Laboratory, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Methods 27:150-5. 2002..We have demonstrated that this technique is a rapid and efficient method that can be used to screen for altered methylation patterns in genomic DNA and to isolate specific sequences associated with these changes...
Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cellsJonathan C Cheng
Department of Urology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9181, USA
Mol Cell Biol 24:1270-8. 2004..Last, sequential treatment with 5-aza-2'-deoxycytidine followed by zebularine hindered the remethylation of the p16 5' region and gene resilencing, suggesting the possible combination use of both drugs as a potential anticancer regimen...
Targeting DNA methylation for epigenetic therapyXiaojing Yang
Department of Urology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Trends Pharmacol Sci 31:536-46. 2010..This review delineates the latest cancer epigenetic models, the recent discovery of hypomethylation agents as well as their application in the clinic...
Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cellsDaniel J Weisenberger
Urologic Cancer Research Laboratory, Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, 1441 Eastlake Avenue, Room 8302L, Los Angeles, CA 90089 9181, USA
Gene 298:91-9. 2002..The preferential expression of the beta transcript in ES cells suggests that this transcript, in addition to Dnmt3a2, may also be important for de novo methylation during development...
The epigenomics of cancerPeter A Jones
Department of Urology, Biochemistry, and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA
Cell 128:683-92. 2007....
DNA methylation: the nuts and bolts of repressionTina Branscombe Miranda
Department of Urology, Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
J Cell Physiol 213:384-90. 2007..In this review, we will discuss the mechanisms which lead to the long-term silencing of genes and will survey the progression that has been made in determining the targeted mechanisms for de novo DNA methylation...
Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cellsLi Jia
Department of Urology, Norris Cancer Center, USC Keck School of Medicine, Los Angeles, California, USA
Mol Cell Biol 26:7331-41. 2006..These features contribute to the androgen-independent phenotype of these cells...
Cancer epigenetics: modifications, screening, and therapyEinav Nili Gal-Yam
Department of Urology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles 90089, USA
Annu Rev Med 59:267-80. 2008..We review these modifications in normal and cancer cells and the evolving approaches used to study them. Additionally, we outline advances in their potential use for cancer diagnostics and targeted epigenetic therapy...
RUNX3 methylation reveals that bladder tumors are older in patients with a history of smokingErika M Wolff
Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90089, USA
Cancer Res 68:6208-14. 2008..Because RUNX3 methylation is acquired early on in tumorigenesis, then its detection in biopsy or urine specimens could provide a marker to screen cigarette smokers long before any symptoms of bladder cancer are present...
Footprinting of mammalian promoters: use of a CpG DNA methyltransferase revealing nucleosome positions at a single molecule levelMehrnaz Fatemi
Department of Urology, Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California Los Angeles, CA 90089-9181, USA
Nucleic Acids Res 33:e176. 2005..Our high resolution approach gives a 'digitized' visualization of each promoter providing information regarding nucleosome occupancy and may be utilized to define transcription factor binding and chromatin remodeling...
DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLightDaniel J Weisenberger
Department of Surgery, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA
Nucleic Acids Res 36:4689-98. 2008..Using digital MethyLight, we identified single-molecule, cancer-specific DNA hypermethylation events in the CpG islands of RUNX3, CLDN5 and FOXE1 present in plasma samples from breast cancer patients...
Chromatin, cancer and drug therapiesConnie C Cortez
Department of Urology, University of Southern California, Los Angeles, CA 90089 9181, USA
Mutat Res 647:44-51. 2008..Progress has been made in the treatment of hematological malignancies and some solid tumors. As the knowledge of how chromatin regulates gene expression is enhanced, improvements in the treatment of cancer can be made...
Epigenetics and microRNAsJody C Chuang
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles 90089, USA
Pediatr Res 61:24R-29R. 2007..We examine the effects of miRNAs on epigenetic machinery, and the control of miRNA expression by epigenetic mechanisms. Epigenetics is defined as heritable changes in gene expression that do not involve a change in DNA sequence...
Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2'-deoxycytidineGangning Liang
USC Norris Comprehensive Cancer Center, Department of Urology, Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089 9181, USA
Cancer Res 62:961-6. 2002..Interestingly, a high percentage of genes activated in both cell types belonged to the IFN signaling pathway, confirming data from other tumor cell types...
Discovery of epigenetically masked tumor suppressor genes in endometrial cancerNoriyuki Takai
Division of Hematology/Oncology, Cedars-Sinai Medical Center/University of California at Los Angeles School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA
Mol Cancer Res 3:261-9. 2005..Our data suggest that C/ebpalpha and Tig1 function as tumor suppressor proteins in endometrial cancers and that their reexpression may be a therapeutic target...
p53 gene and protein status: the role of p53 alterations in predicting outcome in patients with bladder cancerBen George
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA
J Clin Oncol 25:5352-8. 2007..This study evaluated the clinical relationship of the p53 gene and protein statuses...
Functional DNA demethylation is accompanied by chromatin accessibilityKurinji Pandiyan
Department of Urology, Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033 USA, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Program in Human Genetics, 21231, USA and Program in Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA, USA
Nucleic Acids Res 41:3973-85. 2013....
Epigenetic therapy of cancer: past, present and futureChristine B Yoo
USC/Norris Comprehensive Cancer Center, Department of Urology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, California 90089, USA
Nat Rev Drug Discov 5:37-50. 2006....
Epigenetics in human disease and prospects for epigenetic therapyGerda Egger
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Room 8302L, Los Angeles, California 90089-9181, USA
Nature 429:457-63. 2004....
Origins of bidirectional promoters: computational analyses of intergenic distance in the human genomeDaiya Takai
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA
Mol Biol Evol 21:463-7. 2004..This exclusion might be responsible for the existence of these divergent transcripts...
Epigenetic activation of tumor suppressor microRNAs in human cancer cellsYoshimasa Saito
Department of Urology, Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA
Cell Cycle 5:2220-2. 2006..Activation of tumor suppressor miRNAs by chromatin modifying drugs may cause downregulation of target oncogenes and could be a novel strategy for the prevention and treatment of human cancer...
DNA methylation and cancerPhillippa C Taberlay
Department of Urology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
Prog Drug Res 67:1-23. 2011..Here, we will discuss the importance of both established and novel molecular concepts that may underlie the role of DNA methylation in cancer...
Differentially methylated alleles in a distinct region of the human interleukin-1alpha promoter are associated with allele-specific expression of IL-1alpha in CD4+ T cellsJohanna G I van Rietschoten
Department of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Rm 7341, Los Angeles, CA 90089 9181, USA
Blood 108:2143-9. 2006..Taken together, these results suggest that allele-specific expression of IL-1alpha in CD4+ cells is achieved, at least in part, by differential methylation of the promoter...
Epigenetics in cancerShikhar Sharma
Department of Urology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9181, USA
Carcinogenesis 31:27-36. 2010....
Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cellsShikhar Sharma
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089 9181, USA
Epigenetics Chromatin 5:3. 2012..abstract:..
Methylation-sensitive single-molecule analysis of chromatin structureTina B Miranda
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA
Curr Protoc Mol Biol . 2010..SssI), followed by bisulfite sequencing of individual progeny DNA molecules. Unlike nuclease-based approaches, this method allows each molecule to be viewed as an individual entity instead of an average population...
The potential prognostic, predictive, and therapeutic values of DNA methylation in cancer. Commentary re: J. Kwong et al., Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin. Cancer Res., 8: 131-137, 2002, and H-Z. Zou et al., DMartin Widschwendter
University of Southern California/Norris Comprehensive Cancer Center, Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9181, USA
Clin Cancer Res 8:17-21. 2002
MicroRNAs: critical mediators of differentiation, development and diseaseJeffrey M Friedman
Department of Urology, Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Swiss Med Wkly 139:466-72. 2009..Moreover, many disease states, including cancer, occur or are sustained by miRNA dysregulation. In this article, the latest reports of miRNA involvement and aberrant expression in human disease are reviewed, with an emphasis on cancer...
Quantitative methylation analysis using methylation-sensitive single-nucleotide primer extension (Ms-SNuPE)Mark L Gonzalgo
Department of Biochemistry and Molecular Biology, Urologic Cancer Research Laboratory, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90089-9181, USA
Methods 27:128-33. 2002..The Ms-SNuPE technique can be adapted for high-throughput methylation analysis and therefore represents a novel approach for rapid quantitation of cytosine methylation suitable for a wide range of biological investigations...
Comprehensive analysis of CpG islands in human chromosomes 21 and 22Daiya Takai
Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA
Proc Natl Acad Sci U S A 99:3740-5. 2002..This finding is compatible with the recent detection of 5-methylcytosine in Drosophila, and might suggest that S. cerevisiae has, or once had, CpG methylation...
Rethinking how DNA methylation patterns are maintainedPeter A Jones
Peter A Jones and Gangning Liang are at the Department of Urology, Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089 9181, USA
Nat Rev Genet 10:805-11. 2009....
The DNA methylation paradoxP A Jones
Department of Biochemistry and Molecular Biology, University of Southern, California Norris Comprehensive Cancer Center and Hospital, Los Angeles 90033 0800, USA
Trends Genet 15:34-7. 1999..The methylation paradox might be resolved if it is hypothesized that transcription through a CpG island facilitates de novo methylation...
Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylationC T Nguyen
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Room 8302L, Los Angeles, CA 90089-9181, USA
Nucleic Acids Res 29:4598-606. 2001....
Cancer epigenetics comes of ageP A Jones
Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, The Norris Comprehensive Cancer Center, Los Angeles 90033, USA
Nat Genet 21:163-7. 1999..We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation...
The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cellsG Liang
Department of Biochemistry and Molecular Biology, University of Southern California Norris Comprehensive Cancer Center, School of Medicine, Los Angeles 90033, USA
Cancer Res 60:4907-12. 2000..Our results suggest that potential tumor suppressor genes can be isolated from human tumors by virtue of their altered methylation patterns...
Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPCJ M Van Tornout
Department of Pediatrics, JSC Norris Comprehensive Cancer Center, University of Southern California School of Medicine, Los Angeles 90033 0800, USA
Cancer Epidemiol Biomarkers Prev 6:493-7. 1997..This is the first report investigating the presence of p53 missense mutations in NPC among a low-risk population. Our data indicate that p53 is also an infrequent event among NPC patients at low risk for the disease...
The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cellsM M Pao
Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA 90089-9176, USA
Hum Mol Genet 10:903-10. 2001....
Novel endothelin B receptor transcripts with the potential of generating a new receptorM Tsutsumi
Department of Biochemistry and Molecular Biology, Urologic Cancer Research Laboratory USC Norris Comprehensive Cancer Center, University of Southern California, School of Medicine, Los Angeles, CA 90033, USA
Gene 228:43-9. 1999..These transcripts are widely expressed in human tissues, but their expression patterns vary between different tissues...
Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elementsGangning Liang
USC/Norris Comprehensive Cancer Center, Department of Urology, Keck School of Medicine of the University of Southern California, Los Angeles, California 90089-9181, USA
Mol Cell Biol 22:480-91. 2002..Our results reveal a previously unrecognized degree of cooperativity among mammalian DNA methyltransferases in ES cells...
DNA methylation and cellular reprogrammingDaniel D De Carvalho
Department of Urology, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Trends Cell Biol 20:609-17. 2010..Elucidation of the epigenetic changes taking place during cellular reprogramming will enhance our understanding of stem cell biology and facilitate therapeutic applications...
DNA methylation and breast carcinogenesisMartin Widschwendter
USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, MS 8302L, Los Angeles, California, CA 90089 9181, USA
Oncogene 21:5462-82. 2002....
Tissue-specific alternative splicing in the human INK4a/ARF cell cycle regulatory locusK D Robertson
USC Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA
Oncogene 18:3810-20. 1999..The implications of the capacity of the INK4a/ARF locus to encode a third transcript, and for pancreatic cancer, in which the INK4a/ARF locus is nearly always altered, are considered...
Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cellsC Nguyen
Department of Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine of the USC, Los Angeles, USA
J Natl Cancer Inst 93:1465-72. 2001..Subsequent selection of cells with a growth advantage conferred by spread of methylation into and inactivation of a particular promoter might then contribute to the genesis of a specific type of cancer...
Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cellsM F Chan
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, 90089-9176, USA
Mol Cell Biol 21:7587-600. 2001..We conclude that Dnmt1 deficiency and the accompanying genomic DNA hypomethylation result in a reduction of three major pathways of gene inactivation in our model system...
Mismatch repair deficiency and CpG island hypermethylation in sporadic colon adenocarcinomasZ Xiong
Departments of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA 90089-9176, USA
Cancer Epidemiol Biomarkers Prev 10:799-803. 2001....
The CpG island searcher: a new WWW resourceDaiya Takai
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, Los Angeles, USA
In Silico Biol 3:235-40. 2003..The CpG Island Searcher is available on the World Wide Web at http://www.cpgislands.com or http://www.uscnorris.com/cpgislands/cpg.cgi...
Establishment of conditional vectors for hairpin siRNA knockdownsShiro Matsukura
Department of Biochemistry and Molecular Biology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Nucleic Acids Res 31:e77. 2003..Removal of the inducer, doxycycline, from treated cells led to re-expression of the targeted gene. Thus the method allows for a highly controlled approach to gene knockdown...
Zebularine: a new drug for epigenetic therapyC B Yoo
Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, 1441 Eastlake Ave, Los Angeles, CA 90089-9176, USA
Biochem Soc Trans 32:910-2. 2004..Further studies exploring the effectiveness of zebularine in a variety of settings could allow the development of novel therapies for cancer...
The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumorsK D Robertson
University of Southern California, Norris Comprehensive Cancer Center, MS 83, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Nucleic Acids Res 27:2291-8. 1999..Lastly, several novel alternatively spliced forms of DNMT3b, which may have altered enzymatic activity, were found to be expressed in a tissue-specific manner...
Coordinate regulation of Igf-2 and H19 in cultured cellsP Eversole-Cire
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California, School of Medicine, Los Angeles 90033, USA
Cell Growth Differ 6:337-45. 1995..The data provide new experimental evidence for previously hypothesized mechanisms suggesting that Igf-2 and H19 are coordinately regulated...
Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over timeI D Markl
Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
Cancer Res 61:5875-84. 2001....
Large scale mapping of methylcytosines in CTCF-binding sites in the human H19 promoter and aberrant hypomethylation in human bladder cancerD Takai
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
Hum Mol Genet 10:2619-26. 2001..Loss of methylation imprinting of H19 is linked to hypomethylation of the paternal allele in human bladder cancer, unlike the situation in Wilms' tumor and colon cancer where the maternal allele becomes hypermethylated...
Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancerErika M Wolff
Department of Biochemistry, University of Southern California, Los Angeles, CA 90089, USA
Nat Clin Pract Urol 2:502-10. 2005..This review examines the published data and proposes a model for the mechanisms behind bladder cancer development...
Expression of H19 does not influence the timing of replication of the Igf2/H19 imprinted regionC Q Windham
Department of Biochemistry and Molecular Biology, USC Norris Comprehensive Cancer Center, Los Angeles, USA
Dev Genet 20:29-35. 1997..This indicates that any differences in the timing of replication at the Igf2/H19 locus are of a lesser magnitude than those found in other imprinted regions...
Meddling with methylationChih-Lin Hsieh
Nat Cell Biol 5:502-4. 2003
Epigenetic changes in cancerKirsten Grønbaek
Department of Hematology, Rigshospitalet, Copenhagen, Denmark
APMIS 115:1039-59. 2007....
Inhibition of DNA methylation and reactivation of silenced genes by zebularineJonathan C Cheng
University of Southern California/Norris Comprehensive Cancer Center and Hospital, Department of Biochemistry and Molecular Biology, USC Keck School of Medicine, Los Angeles 90089, USA
J Natl Cancer Inst 95:399-409. 2003..001) or by oral gavage (P<.001). CONCLUSIONS: Zebularine is a stable DNA demethylating agent and the first drug in its class able to reactivate an epigenetically silenced gene by oral administration...
Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapyVictor E Marquez
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute at Frederick, NIH, Frederick, Maryland 21702, USA
Ann N Y Acad Sci 1058:246-54. 2005..The latter activity makes zebularine a promising antitumor agent that is hydrolytically stable, preferentially targets cancer cells, and shows activity both in vitro and in experimental animals, even after oral administration...
Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatmentMichael Daskalakis
Department of Hematology, University of Freiburg Medical Center, Freiburg, Germany
Blood 100:2957-64. 2002....
Zebularine: a unique molecule for an epigenetically based strategy in cancer chemotherapy. The magic of its chemistry and biologyVictor E Marquez
Laboratory of Medicinal Chemistry, Center for Cancer Research, NCI at Frederick, NIH, Frederick, MD 21702, USA
Nucleosides Nucleotides Nucleic Acids 24:305-18. 2005..Zebularine is a stable, antitumor agent that preferentially targets cancer cells and shows activity both in vitro and in experimental animals, even after oral administration...
Moving AHEAD with an international human epigenome projectPeter A Jones
Nature 454:711-5. 2008
Hyperphosphorylation of pRb: a mechanism for RB tumour suppressor pathway inactivation in bladder cancerSunanda J Chatterjee
Department of Pathology, USC/Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA
J Pathol 203:762-70. 2004..Immunohistochemical expression of pRb appears to be a reliable indicator of pRb function...
Association of breast cancer DNA methylation profiles with hormone receptor status and response to tamoxifenMartin Widschwendter
Department of Urology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Los Angeles, California, 90089-9176, USA
Cancer Res 64:3807-13. 2004....
Research Grants
- MOLECULAR MECHANISMS OF HUMAN BLADDER CARCINOGENESISPeter Jones; Fiscal Year: 2006..The participating investigators have a considerable history of collaboration in the areas of translational research in the field of bladder cancer and these interactions will be formalized and enhanced by this Program Project Grant. ..
- TRAINING PROGRAM IN VIRAL AND CHEMICAL CARCINOGENESISPeter Jones; Fiscal Year: 2007....
