We propose to operate a Genome Characterization Center for The Cancer Genome Atlas (TCGA) of the National Cancer Institute. Our goal is to characterize the genomes and transcriptomes of 10,000 human cancers over 5 years, together with the collaborators of TCGA Research Network. Given the ongoing revolution in genome analysis, our Center will transition from current-generation microarray technologies to next-generation sequencing technologies for cancer genome characterization. We will accomplish this by benchmarking the next-generation technologies against state-of-the-art array technologies used in the pilot project of TCGA. Our Center is uniquely qualified for this effort, because of our expertise in next-generation sequencing as well as current-generation microarray production and technology development, our knowledge and demonstrated accomplishments in cancer genomics, and our commitment to and experience with multi-institutional collaborations including the pilot project of TCGA. Specifically, we intend to accomplish the following aims for TCGA:
Aim 1. Using microarray technologies: Characterize DNA and RNA from 2000 cancer samples and appropriate controls during year 1.
Aim 2. Using next-generation sequencing: (i) Perform direct comparison and validation of the three alternative platforms during year 1, by characterizing DNA from 300 cancer/normal sample pairs and RNA from 100 cancer samples. (ii) Select the most cost-effective sequencing platform at the end of year 1, based on the results and in conjunction with NCI staff. (iii) Implement this sequencing platform to characterize DNA and RNA from 2000 cancer samples and appropriate controls in Years 2-5. (iv) Continue to decrease cost and increase resolution of genomic analysis.

Public Health Relevance

Cancer is a genomic disease, caused by somatic and germ-line alterations in DNA and RNA. By discovering and enumerating these alterations, we can improve the diagnosis and treatment of cancer: this is the goal of The Cancer Genome Atlas. Our proposed Genome Characterization Center could contribute significantly to TCGA by advancing genomic technology and by rapidly accomplishing cancer genome discoveries.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
3U24CA143867-05S1
Application #
8925190
Study Section
Special Emphasis Panel (ZCA1-SRLB-U (O1))
Program Officer
Tarnuzzer, Roy W
Project Start
2009-09-29
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2015-07-31
Support Year
5
Fiscal Year
2014
Total Cost
$860,863
Indirect Cost
$326,233
Name
Broad Institute, Inc.
Department
Type
DUNS #
623544785
City
Cambridge
State
MA
Country
United States
Zip Code
02142
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Cancer Genome Atlas Research Network (2015) The Molecular Taxonomy of Primary Prostate Cancer. Cell 163:1011-25
(2015) Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N Engl J Med 372:2481-98
Zhang, Cheng-Zhong; Adalsteinsson, Viktor A; Francis, Joshua et al. (2015) Calibrating genomic and allelic coverage bias in single-cell sequencing. Nat Commun 6:6822
Cancer Genome Atlas Network (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517:576-82
Cancer Genome Atlas Network (2015) Genomic Classification of Cutaneous Melanoma. Cell 161:1681-96

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