We are seeking support to establish a Genome Characterization Center, as a part of the Cancer Genome Atlas Project in Boston. The goal of the proposed effort is to analyze 2,000-2,500 tumor samples each year over a five-year period of time and identify a set of genes that can be resequenced by the members of The Cancer Genome Atlas (TCGA) project. It is well established that regions of the cancer genome that are amplified or show loss of heterozygosity or deletion harbor genes that are important for tumor initiation and progression. We will initially identify such regions in the cancer genome by conducting array comparative genomic hybridization (aCGH). Based upon detailed comparisons of many different platforms we have chosen to use the high-density Agilent oligonucleotide arrays for our studies. We have used the Agilent platform to characterize several hundreds of tumors and their corresponding controls, much of it a part of the current TCGA project. We already have the ability to have a throughput of processing four to five thousand samples during the first year of the proposed grant. During the first year we propose to use a sequencing based approach to determine copy number changes in tumors. In the initial phase we will examine 200 samples by a sequence tag counting approach and compare the results with the Agilent and other platforms. Based upon our experience we anticipate that this is eminently feasible and we will gradually switch the copy number analysis to the sequence based platform. In the second year 40% of the samples will be processed by the sequencing platform and the remaining 60% by the array platform. In year three 60% of the samples will be processed by sequencing and in years 4 and 5 we plan to completely switch to the sequencing approach. We have a well established pipeline to collect, store, retrieve and analyze the data from these two platforms. We will develop Level 1-4 data as defined by the consortium and deposit these data in a timely fashion in the Data Coordinating Center. We also propose to use powerful informatics tools that we have developed and propose to improve to analyze the aCGH and the sequence based data and extract a list of most interesting genes for resequencing. We have established an award winning IT infrastructure that will be deployed for LIMS, data storage, data retrieval, data analysis and interface with caBIG. Our proposed approach also has the ability to generate additional useful data for tumor and patient stratification.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24CA144025-03
Application #
8124973
Study Section
Special Emphasis Panel (ZCA1-SRLB-U (O1))
Program Officer
Lee, Jerry S
Project Start
2009-09-29
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
3
Fiscal Year
2011
Total Cost
$2,061,165
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Sun, Yan; Ji, Ping; Chen, Tao et al. (2017) MIIP haploinsufficiency induces chromosomal instability and promotes tumour progression in colorectal cancer. J Pathol 241:67-79
Cherniack, Andrew D; Shen, Hui; Walter, Vonn et al. (2017) Integrated Molecular Characterization of Uterine Carcinosarcoma. Cancer Cell 31:411-423
Cancer Genome Atlas Research Network. Electronic address: elizabeth.demicco@sinaihealthsystem.ca; Cancer Genome Atlas Research Network (2017) Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas. Cell 171:950-965.e28
Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat et al. (2017) Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell 171:540-556.e25
Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Analytical Biological Services et al. (2017) Integrated genomic and molecular characterization of cervical cancer. Nature 543:378-384
Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude et al. (2017) Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles. Cell Rep 18:2780-2794
Fishbein, Lauren; Leshchiner, Ignaty; Walter, Vonn et al. (2017) Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma. Cancer Cell 31:181-193
Cancer Genome Atlas Research Network; Analysis Working Group: Asan University; BC Cancer Agency et al. (2017) Integrated genomic characterization of oesophageal carcinoma. Nature 541:169-175
Huo, Dezheng; Hu, Hai; Rhie, Suhn K et al. (2017) Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas. JAMA Oncol 3:1654-1662
Robertson, A Gordon; Shih, Juliann; Yau, Christina et al. (2017) Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. Cancer Cell 32:204-220.e15

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