The USC-JHU Cancer Epigenome Characterization Center
Principal Investigator: Peter W Laird
Abstract: In the past two decades, it has become clear that cancer arises not only as a consequence of genetic events, such as mutations, copy number alterations, and sequence rearrangements, but also as a result of extensive changes to the epigenome. Epigenetic alterations contribute causally to the origin and malignant progression of cancer, and affect clinical outcome. The USC-JHU Cancer Epigenome Characterization Center specializes in the production and analysis of genome-scale cancer epigenetic data. During the pilot phase of The Cancer Genome Atlas, our center has been responsible for the production and deposition of all high-throughput epigenomic data within TCGA. A key outcome of the TCGA pilot was our finding of a link in glioblastoma multiforme between MGMT promoter methylation, treatment with alkylating agents, and a hypermutator phenotype associated with mismatch repair deficiency, an observation with potential clinical implications. For the next phase of TCGA, we propose the following three objectives. Objective 1 is to characterize the DNA methylation status of 27,578 CpG dinucleotides located in 14,495 gene promoters in at least 10,000 human cancer samples and 1,000 control samples using the lllumina Infinium DNA Methylation analysis platform. Objective 2 is to transition epigenomic data production in TCGA to whole genome shotgun bisulfite sequence analysis to provide single-base-pair resolution DNA methylation data for TCGA cancer samples. Objective 3 is to implement quality control and quality assurance measures to ensure that epigenomic data deposited for public dissemination meets rigorous standards. Our group has considerable expertise in cancer epigenomics, with two founders of the field of cancer epigenetics and with members who collectively have pioneered the majority of widely used DNA methylation analysis techniques, and who have provided many of the biological insights. Epigenomic data are a necessary component for a full understanding of the relationship between alterations in the cancer genome and the origin and clinical diversity of individual tumors.
Funding Period: 2009-09-29 - 2014-07-31
more information: NIH RePORT
- Principles and challenges of genomewide DNA methylation analysisPeter W Laird
USC Epigenome Center, University of Southern California, Keck School of Medicine, Los Angeles, 90089 9601, USA
Nat Rev Genet 11:191-203. 2010..This Review discusses the different approaches and their relative merits and introduces considerations for data analysis...
- The somatic genomic landscape of glioblastomaCameron W Brennan
Human Oncology and Pathogenesis Program, Brain Tumor Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, Department of Neurological Surgery, Weill Cornell Medical Center, New York, NY 10065, USA Electronic address
Cell 155:462-77. 2013....
- Integrated genomic characterization of endometrial carcinomaGad Getz
The Eli and Edythe L Broad Institute of Massachusetts Institute of Technology and Harvard University Cambridge, Massachusetts 02142, USA
Nature 497:67-73. 2013..We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours...
- Interplay between the cancer genome and epigenomeHui Shen
USC Epigenome Center, University of Southern California, Room G511B, 1450 Biggy Street, Los Angeles, CA 90089 9061, USA
Cell 153:38-55. 2013..Disruption of epigenomic control is pervasive in malignancy and can be classified as an enabling characteristic of cancer cells, akin to genome instability and mutation...
- Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancerHui Shen
USC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA
Nat Commun 4:1628. 2013..These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes...
- Low-level processing of Illumina Infinium DNA Methylation BeadArraysTimothy J Triche
Department of Preventive Medicine, USC Keck School of Medicine of USC, Los Angeles, CA 90089, USA
Nucleic Acids Res 41:e90. 2013....
- Identification of a CpG island methylator phenotype that defines a distinct subgroup of gliomaHoutan Noushmehr
USC Epigenome Center, University of Southern California, Los Angeles, CA 90033, USA
Cancer Cell 17:510-22. 2010..Patients with G-CIMP tumors are younger at the time of diagnosis and experience significantly improved outcome. These findings identify G-CIMP as a distinct subset of human gliomas on molecular and clinical grounds...
- Epigenetic and Transcriptional Dysregulation in Autism Spectrum DisorderDaniel H Geschwind; Fiscal Year: 2013..In addition, these data will be made available to the community in a web-based format to be of maximum utility. ..
- Methylomic and genomic impacts of organic pollutants in Dup15q syndromeJanine M LaSalle; Fiscal Year: 2013..Finally, the results of these studies are expected to be broadly relevant to understanding the relationship between the genome, environmental exposures, and the epigenome in human health and disease. ..
- Novel molecular signatures of colorectal cancerVictoria Valinluck Lao; Fiscal Year: 2013..These studies will provide critical information for identifying and developing biomarkers for more effective treatment of people with CRC. ..
- Jules Stein Eye Institute Core Grant for Vision ResearchWayne L Hubbell; Fiscal Year: 2013..Support in the form of the Core grant is requested to maintain these Modules through instrument service contracts, and to provide necessary personnel support to assist and train users and provide routine maintenance. ..
- Statistical Analysis of Epigenomics DataKimberly D Siegmund; Fiscal Year: 2013....
- Frontotemporal Dementias: Genotypes and PhenotypesVirginia M Lee; Fiscal Year: 2013..elegans and transgenic mouse models. The proposed studies will provide important insights into mechanisms of FTLD and the diagnosis and treatment of these disorders. ..
- Multiscale Mathematical Modeling of Cancer ProgressionVito Quaranta; Fiscal Year: 2013..Finally, we will continue education/outreach efforts, e.g., hands-on cancer modeling workshops, to attract physical and biological scientists, especially the brightest of the new generations. ..
- Elucidating Risks: From Exposure and Mechanism to OutcomeJames A Swenberg; Fiscal Year: 2013..This Program is highly relevant to Superfund by addressing high-priority chemicals and by focusing on mechanisms underlying health effects, exposure assessment, and remediation to mitigate exposure and toxicity. ..
- Interrogating Epigenetic Changes in Cancer GenomesTim H M Huang; Fiscal Year: 2013..abstract_text> ..
- PAPOVA VIRUS TRANSFORMING MECHANISMSDAVID MORSE LIVINGSTON; Fiscal Year: 2013..The goal of this Program is to continue to shed new light on cellular transformation events that also underpin human cancer development and generate insights that lead to new cancer therapeutic strategies. ..