Our objective is to establish and operate a high throughput Genome Characterization Centre (GCC) that specializes in sequencing libraries, prepared from mRNAs and microRNAs purified from cancer cells and tissues. To achieve our objective, we will build upon existing """"""""next generation"""""""" sequencing and analysis strengths at the BC Genome Sciences Centre. We have accumulated world-leading experience in the operation of lllumina sequencers as a consequence of becoming one of the four Early Access Partners originally engaged by Solexa (now lllumina) in November of 2006. Since then, we have led in the development and implementation of protocols for preparing and sequencing numerous library types on the lllumina GA platform, including both microRNA and mRNA libraries. To build sequencing libraries, we have established an lllumina library construction core that has constructed 1,075 libraries, from which we have generated more than 934 billion base-pairs of high quality sequence information. These data have so far provided the basis for 19 publications describing results obtained from sequencing genomes and transcriptomes, and describing the creation of new software tools and algorithms to manage and analyze the wealth of data such instruments produce. To develop and critically appraise instrument upgrades, new instruments and new protocols, we have established a next generation technology development core. Technologies developed and appraised by this group are approved for use by our lllumina production sequencing core. Under-pinning this enterprise is a formal system for quality assurance and quality control that encompasses laboratory and bioinformatics activities, and a laboratory information management system that regulates and monitors laboratory activity, inventory, and features real time error avoidance. Our experience in assembling these teams and this infrastructure will serve as a basis for scaling up our library production capacity to meet our objectives, which are to sequence 4,400 transcriptome libraries in the first year of our operation. Using bioinformatics tools already in production, we will analyze these sequences to profile the expression of genes, individual exons and microRNAs, and analyze the sequences to discover mutations and RNA editing events in expressed sequences. These analyses will provide an unprecedented view of transcription in cancer cells;identify promising new mutated and expressed therapeutic targets, and identify genes and pathways that are drivers of oncogenesis.

Public Health Relevance

Mutations and other perturbations in genes can cause cancer, or affect the way patients respond to cancer treatments. We aim to develop a deep understanding of the cancer genes that are mutated or inappropriately turned on, or off, in cancer cells. We will do this using a powerful new DNA analysis tool called next generation sequencing, to analyze thousands of genes from thousands of cancer samples.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Resource-Related Research Projects--Cooperative Agreements (U24)
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Special Emphasis Panel (ZCA1-SRLB-U (O1))
Program Officer
Tarnuzzer, Roy W
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British Columbia Cancer Agency
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V5 1-L3
Cancer Genome Atlas Research Network; Linehan, W Marston; Spellman, Paul T et al. (2016) Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma. N Engl J Med 374:135-45
Zheng, Siyuan; Cherniack, Andrew D; Dewal, Ninad et al. (2016) Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma. Cancer Cell 29:723-36
Camargo, M Constanza; Bowlby, Reanne; Chu, Andy et al. (2016) Validation and calibration of next-generation sequencing to identify Epstein-Barr virus-positive gastric cancer in The Cancer Genome Atlas. Gastric Cancer 19:676-81
Ceccarelli, Michele; Barthel, Floris P; Malta, Tathiane M et al. (2016) Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell 164:550-63
Chu, Andy; Robertson, Gordon; Brooks, Denise et al. (2016) Large-scale profiling of microRNAs for The Cancer Genome Atlas. Nucleic Acids Res 44:e3
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
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
Cancer Genome Atlas Research Network (2014) Comprehensive molecular profiling of lung adenocarcinoma. Nature 511:543-50

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