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International network of cancer genome projects
Associated Data
Abstract
The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumors from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of over 25,000 cancer genomes at the genomic, epigenomic, and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically-relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
The genomes of all cancers accumulate somatic mutations1. These include nucleotide substitutions, small insertions and deletions, chromosomal rearrangements and copy number changes that can affect protein-coding or regulatory components of genes. In addition, cancer genomes usually acquire somatic epigenetic “marks” compared to non-neoplastic tissues from the same organ, notably changes in the methylation status of cytosines at CpG dinucleotides.
A subset of the somatic mutations in cancer cells confers oncogenic properties such as growth advantage, tissue invasion and metastasis, angiogenesis, and evasion of apoptosis2. These are termed “driver” mutations. The identification of driver mutations will provide insights into cancer biology and highlight novel drug targets and diagnostic tests. Knowledge of cancer mutations has already led to the development of specific therapies, such as trastuzumab for HER2/neu positive breast cancers3 and imatinib, which targets BCR-ABL tyrosine kinase for the treatment of chronic myeloid leukemia4,5. The remaining somatic mutations in cancer genomes that do not contribute to cancer development are called “passengers”. These mutations provide insights into the DNA damage and repair processes that have been operative during cancer development, including exogenous environmental exposures6,7. In most cancer genomes, it is anticipated that passenger mutations, as well as germline variants not yet catalogued in polymorphism databases, will substantially outnumber drivers.
Large-scale analyses of genes in tumors have revealed that the mutation load in cancer is abundant and heterogeneous8-13. Preliminary surveys of cancer genomes have already demonstrated their relevance in identifying new cancer genes that constitute potential therapeutic targets for several types of cancer, including PIK3CA14, BRAF15, NF110, KDR10, PIK3R19, and histone methyltransferases and demethylases16,17. These projects have also yielded correlations between cancer mutations and prognosis, such as IDH1 and IDH2 mutations in several types of gliomas13,18. Advances in massively parallel sequencing technology have enabled sequencing of entire cancer genomes 19-22.
Following the launch of comprehensive cancer genome projects in the United Kingdom (Cancer Genome Project)23 and the United States (The Cancer Genome Atlas)24, cancer genome scientists and funding agencies met in Toronto (Canada) in October 2007 to discuss the opportunity to launch an international consortium. Key reasons for its formation were: (1) the scope is huge; (2) independent cancer genome initiatives could lead to duplication of effort or incomplete studies; (3) lack of standardization across studies could diminish the opportunities to merge and compare datasets; (4) the spectrum of many cancers is known to vary across the world; (5) an international consortium will accelerate the dissemination of datasets and analytical methods into the user community.
Working groups were created to develop strategies and policies that would form the basis for participation in the ICGC. The goals of the Consortium (Box 1) were released in April 2008 (http://www.icgc.org/files/ICGC_April_29_2008.pdf). Since then, working groups and initial member projects have further refined the policies and plans for international collaboration.
Bioethical Framework
ICGC members agreed to a core set of bioethical elements for consent as a precondition of membership (Box 2). The Ethics and Policy Committee has created patient consent templates for both prospective collection and retrospective use of samples and data for ICGC projects. Differences in project-specific requirements and national legal frameworks may require some local amendments, while still reflecting the core principles of ICGC.
The ICGC recognizes a delicate balance between protecting participants' personal data and sharing these data to accelerate cancer research. Data access policies have been drawn up that are respectful of the rights of the donors, while allowing ICGC data derived from samples to be shared ethically among a wide research community. Two levels of access have been implemented. For data that cannot be used to identify individuals, “Open access” datasets are publically available. These include data such as gender, age range, histology, normalized gene expression values, epigenetic datasets, somatic mutations, summaries of germline data, and study protocols. “Controlled access” datasets contain germline genomic data and detailed clinical information that are associated to a unique individual whose personal identifiers have been removed. To access controlled datasets researchers must seek authorizations by contacting the Data Access Compliance Office (DACO) (http://www.icgc.org/daco). An independent International Data Access Committee (IDAC) oversees the work of the DACO and provides assistance with resolving issues that arise.
Pathology and Clinical Annotation
Large-scale genomic studies of human tumors rely on the availability of fresh frozen tumor tissue. To address the paucity of samples that meet ICGC standards, many projects have initiated prospective collections of high quality source material. Accordingly, the ICGC recommended procedures to promote consistency of sample processing throughout the Consortium and ensure a series of quality features such as high tissue integrity and tumor cell content. Each project will need to include diverse data types such as environmental exposures, clinical history of participants, tumor histopathology, and clinical outcomes.
Tumors display considerable clinical and biological heterogeneity which has resulted in a variety of tumor classifications. Within the ICGC, special measures are taken to promote the consistency of diagnosis. These include the coordination of diagnostic criteria among groups investigating tumors that are related, and policies that all samples will be reviewed by at least two independent reference pathologists. Furthermore, images of the stained tumor sections (or blood smear or cytospins for hematological neoplasias), from which diagnoses were made, will be stored and made available to the community.
Although different tumor types may require specific procedures for tumor acquisition or compilation of clinical and environmental data, ICGC has set guidelines regarding the use of common definitions and data standards. This will allow ICGC data users to identify correlations between tumor-specific molecular changes with clinical and histopathological data including prognosis, prediction of therapy response and tumor classification schemes for diagnosis.
Study Design and Statistical Issues
To identify cancer-related genes, one needs to detect genes that are mutated at a higher frequency than the background mutation rate. Given that several driver genes have been found to be mutated at low frequencies, ICGC will identify somatic mutation observed in at least 3% of tumors of a given subtype. ICGC determined that 500 samples would be needed per tumor type (although for rare tumor types, a smaller sample size may be justified). In practice, the degree of heterogeneity of a given tumor type is difficult to know in advance, such that some particularly heterogeneous tumor types may require larger sample collections.
Cancer Genome Analyses
High-quality catalogues of somatic mutations from whole cancer genomes will ultimately be the ICGC standard. Shotgun sequencing employing second generation technologies can detect all classes of somatic mutation implicated in cancer. Moreover, if the level of coverage is sufficient, comprehensive high quality catalogues of somatic mutations from individual cancer genomes can be acquired with >90% sensitivity and >95% specificity. In order to achieve this, it will be necessary to sequence both the genome of the cancer and of a normal tissue from the same individual to distinguish germline variants. Although a few genomes of this standard have already been generated, the cost and the continuing technology development will mean that interim analyses of particularly informative sectors of the genome will be carried out, for example of all coding exons and microRNAs.
For each individual cancer genome, the catalogue of somatic mutations will be supplemented by genome-wide information on the state of methylation of CpG dinucleotides. The optimal strategies and technologies to achieve this are not yet clear. Moreover, the genomes of individual cancers will be accompanied, where possible, by analyses of the transcriptome. Although conventional array-based approaches currently predominate, it is preferable that RNA sequencing becomes the standard as sequencing has a greater dynamic range25 and provides additional information including novel transcripts and sequence variants26.
ICGC Datasets
The distributed nature of the Consortium coupled with the large size of the datasets makes it cumbersome to store all data in a single centralized repository. For this reason, the ICGC has adopted a “franchise” database model for integrating the information and making it available to the public. Under this model, each member project releases tumor information by copying it into its local franchise database after it has been quality checked. Each franchise database shares a common schema to describe the specimens, the associated clinical information, and their genome characterization data. ICGC primary data files, including sequencing traces, are sent to the National Center for Biotechnology Information (NCBI) and/or the European Bioinformatics Institute (EBI) for archiving, while interpreted data sets, such as somatic mutation calls, are stored in franchise databases. The ICGC franchise databases and web portal use BioMart27, a data federation technology originally developed for use in Ensembl28, and since adopted for use by multiple model organism and genome databases. The management of the ICGC data flow is the responsibility of the ICGC Data Coordination Center (DCC) located at the Ontario Institute for Cancer Research.
The DCC also operates the ICGC data portal which allows researchers to access both Open and Controlled access portions of the ICGC data. The portal provides a variety of user interfaces that range from simple gene-oriented queries (“Show me all the non-silent coding mutations identified in PIK3R1 for all cancers.”) to queries that integrate genomic, clinical, and functional information (“Show me all members of the toll receptor pathway having deletions in stage III breast cancer.”). These queries will be distributed across the franchise databases in a manner that is invisible to the user. The portal will also provide links to the primary files at NCBI and EBI, interfaces for generating tabular reports, data dumps in common bioinformatics formats, and other visualizations including genome browser tracks, pathway diagrams and survival curves. The portal is available via a link at http://www.icgc.org.
At the time of this publication, the following cancer and reference datasets will be available through the ICGC web portal:
- Initial data releases from ICGC members for breast cancer (UK), liver cancer (Japan), and pancreatic cancer (Australia and Canada);
- A whole genome dataset of a metastatic melanoma cell line (COLO829)6;
- Open datasets from the TCGA for glioblastoma multiforme (GBM) and serous cystadenocarcinoma of the ovary (see below);
- Links to the human reference genome (http://www.genomereference.org/) and gene annotations from the GENCODE Project (http://www.sanger.ac.uk/gencode/) which includes the CCDS gene set29;
- Links to Reactome32, a curated database of biological pathways in human;
- A set of reference gene models, mirrored from ENSEMBL28.
The current version of the web portal provides an entry point to the open access data tier via interactive query as well as bulk download of data files. We expect that in mid 2010 both open access and controlled data will be available.
The ICGC recently established a bioinformatics analysis working group to compare pipelines, analytic methods, consistency within and among algorithms, and establish guidelines or best practices for the Consortium. Over time, significant resources will be deployed to develop strategies to analyze the large complex datasets generated by ICGC member projects, and provide value-added views of cancer genomic data by integrating them with other biological and epidemiological datasets.
Data Release and IP Policies
The data release policies of the ICGC are intended to maximize public benefit while, at the same time, protecting the interests and rights of sample donors and their relatives. Members of the ICGC are committed to the principles of rapid data release (with appropriate controlled access mechanisms), in concordance with the Toronto Statement33. ICGC members encourage the scientific community to use any data that targets specific genes and mutations, without any restrictions. In order to allow ICGC members the opportunity to be the first to publish global analyses from datasets they generate, the Consortium has also agreed that member projects may specify conditions that include a time limit during which other data users are asked to refrain from publishing global analyses (defined by several ICGC member projects as 100 tumors and matched controls), a provision referred to as a “publication moratorium”. In order to allow time for a dataset to be analyzed and submitted for publication, ICGC members will have at most one year after released datasets reach the specified threshold before third parties are permitted to submit manuscripts describing global analyses. Further details on data release guidelines for data producers, users and reviewers are available http://www.icgc.org. Users of ICGC data are expected to respect these terms and to cite this manuscript and the source of pre-publication data, including the version of the dataset. In cases of uncertainty, scientists using ICGC data are encouraged to contact the member projects to discuss publication plans.
ICGC members believe that maximum public benefit will be achieved if the data remain publicly accessible without patent restrictions hence no claims to possible intellectual property (IP) derived from primary data (including somatic mutations) will be made. Users of ICGC data (including ICGC members) may elect to perform further research and to exercise their IP rights on these downstream discoveries. If this occurs, users are expected to implement licensing policies that do not obstruct further research.
Initial ICGC Projects
Currently nine countries and two European consortia have initiated cancer genome projects under the umbrella of the ICGC. The initial projects, listed in an online table that accompanies this article, will analyze tumor types found around the globe and throughout the human body affecting a diversity of organs including blood, brain, breast, kidney, liver, pancreas, stomach, oral cavity, and ovary. Over time, the ICGC will investigate fifty or more types and subtypes of cancer in adults and children. In the case of tumors with multiple subtypes, analyses should be focused on subtypes that may be defined on pathological, molecular, etiological or geographical differences. It is expected that some cancer types will be studied in parallel in different parts of the world, as the mutation profiles may differ among populations. The consortium has enabled the coordination of initial projects analyzing similar cancers in different countries, and in some cases, the redirection of resources to launch new projects.
The Cancer Genome Atlas (TCGA)
TCGA is a comprehensive program in cancer genomics that is jointly supported and managed by the National Cancer Institute and the National Human Genome Research Institute of the U.S. National Institutes of Health. TCGA began in 2006 as a pilot focused on three projects, glioblastoma multiforme (GBM), serous cystadenocarcinoma of the ovary, and lung squamous carcinoma, and has recently expanded to produce comprehensive genomic data sets for at least 10 additional cancers in the next two years. Given TCGA's contributions in launching the ICGC and cooperation to ensure that its policies (posted at http://cancergenome.nih.gov) are coordinated with those of the ICGC, TCGA's participation in the ICGC is considered to be equivalent to that of a full member. TCGA, however, is not able to join the ICGC formally at this time, because of technical and legal issues in the U.S. related to the mechanisms of the distribution of controlled-access data, although such data are directly available to investigators at http://cancergenome.nih.gov/dataportal. The National Institutes of Health policies relating to distribution of controlled-access datasets are being reviewed with the intent of enabling researchers to integrate and analyze across databases, for example, using the franchise model adopted by the ICGC. Meanwhile, TCGA is ensuring that projects are coordinated and data sets are compatible with those of the Consortium.
ICGC in the Next Decade
A large proportion of common cancers affecting patients around the world have been or will soon be selected for comprehensive cancer genome studies. Further efforts will be needed to leverage support and expertise to tackle the remaining tumor types, including rare cancers. The challenges of the ICGC are daunting due to the scope of the initiative, the complexity that is inherent to the heterogeneity of cancer and the limitations of current technologies to provide accurate long-range assemblies of highly rearranged chromosomes found in tumor cells. These challenges underscore the importance of continued international coordination and further engagement of the scientific community in the next decade.
Moving Towards Clinical Applications
ICGC catalogues, which are expected to grow exponentially, will have immediate relevance in the cancer research community. Early insight into the biology of somatic mutations will come from functional studies in cell-based and animal models of tumors. Mutation screens in retrospective tumor banks linked to registries or clinical trials having significant clinical data will inform on the potential clinical utility of somatic mutations as biomarkers for prognosis or drug-response. Germline variants identified by ICGC projects may allow the discovery of genes predisposing to familial malignancies, such as PALB2 and pancreatic cancer12,34. High throughput screens of RNAi or small molecule libraries, and the adaptation of existing model systems, will play a major role in refining potential therapeutic candidates for further study35.
Translating these discoveries into clinical practice will require more sophisticated clinical trials that take into account the increases in phenotypic subdivisions, additional coordination to identify subjects having tumors with similar profiles, and increased use of biomarkers, genomic analyses, informatics and other technologies in the clinical development of new therapeutics. Given the tremendous potential for relatively low-cost genomic sequencing to reveal clinically useful information, we anticipate that in the not so distant future, partial or full cancer genomes will routinely be sequenced as part of the clinical evaluation of cancer patients and as part of their on-going clinical management. The successful and appropriate translation of cancer genome research into clinical practice will raise important social and ethical questions. It will be essential to combine the expertise of oncologists, biostatisticians, pathologists, geneticists, policy-makers and members of the biopharmaceutical industry to meet this challenge by developing new policies and clinical paradigms that enable rapid translation of many new biomarkers and cancer targets into new clinical tests and therapeutic interventions that will benefit cancer patients.
Acknowledgments
We thank research participants who are generously donating samples and data, as well as physicians and clinical staff contributing to sample annotation and collection. A complete list of organizations that support ICGC projects accompanies this article online.
ICGC Marker Paper Author List As of 10 March 2010
International Cancer Genome Consortium (Project leaders and committee chairs are listed first and are designated with an asterix; other principal investigators and collaborators are listed in alphabetical order or as designated by the project leader).
Executive Committee
Thomas J. Hudson*1,2, Warwick Anderson3, Axel Aretz4, Anna D. Barker5, Cindy Bell6, Rosa R. Bernabé 7, M. K. Bhan8, Fabien Calvo9, Iiro Eerola10, Daniela S. Gerhard5, Alan Guttmacher11, Mark Guyer12, Fiona M. Hemsley13, Jennifer L. Jennings1, David Kerr14,15, Peter Klatt7, Patrik Kolar10, Jun Kusuda16, David P. Lane13, Frank Laplace17, Youyong Lu18, Gerd Nettekoven19, Brad Ozenberger12, Jane Peterson12, T.S. Rao8, Jacques Remacle10, Alan J. Schafer20, Tatsuhiro Shibata21, Michael R. Stratton22, Joseph G. Vockley5, Koichi Watanabe23, Huanming Yang24, Matthew M. F. Yuen25.
Ethics and Policy Committee
Bartha M. Knoppers*26, Martin Bobrow27, Anne Cambon-Thomsen28, Lynn G. Dressler29, Stephanie O. M. Dyke22, Yann Joly26, Kazuto Kato30, Karen L. Kennedy22, Pilar Nicolás31, Michael J. Parker32, Emmanuelle Rial-Sebbag28, Carlos M. Romeo-Casabona31, Kenna M. Shaw5, Susan Wallace26, Georgia L. Wiesner33,34, Nikolajs Zeps35,36.
Tissue and Clinical Annotation Working Group
Peter Lichter*37, Andrew V. Biankin38,39, Christian Chabannon9,40, Lynda Chin41,42, Bruno Clément43, Enrique de Alava44, Françoise Degos45, Martin L. Ferguson46, Peter Geary47, D. Neil Hayes48, Thomas J. Hudson1,2, Amber L. Johns38, Arek Kasprzyk1, Hidewaki Nakagawa49, Robert Penny50, Miguel A. Piris51, Rajiv Sarin52, Aldo Scarpa53,54, Tatsuhiro Shibata21, Marc van de Vijver55,56.
Technologies Working Group
Michael R. Stratton*22, Hiroyuki Aburatani57, Mónica Bayés58,59, David D.L. Bowtell60,61, Peter J. Campbell22,62, Xavier Estivill58,59, P. Andrew Futreal22, Daniela S. Gerhard5, Sean M. Grimmond63, Ivo Gut64, Martin Hirst65, Carlos López-Otín66, Partha Majumder67, Marco Marra65, John D. McPherson1,68, Hidewaki Nakagawa49, Zemin Ning22, Xose S. Puente66, Yijun Ruan69, Tatsuhiro Shibata21, Hendrik G. Stunnenberg70, Harold Swerdlow22, Victor E. Velculescu71, Richard K. Wilson72,73, Hong H. Xue74,75, Liu Yang76.
Bioinformatics Analyses Working Group
Paul T. Spellman*77, Gary D. Bader78,79, Paul C. Boutros1, Peter J. Campbell22,62, Paul Flicek80, Gad Getz81, Roderic Guigó82, Guangwu Guo24, David Haussler83, Simon Heath64, Tim J. Hubbard22, Tao Jiang24, Steven M. Jones65, Qibin Li24, Nuria López-Bigas84, Ruibang Luo24, Lakshmi Muthuswamy1, B. F. Francis Ouellette1, John V. Pearson63, Xose S. Puente66, Victor Quesada66, Benjamin J. Raphael85, Chris Sander86, Tatsuhiro Shibata21, Terence P. Speed87,88, Lincoln D. Stein1, Joshua M. Stuart89, Jon W. Teague22, Yasushi Totoki21, Tatsuhiko Tsunoda49, Alfonso Valencia90, David A. Wheeler91, Honglong Wu24, Shancen Zhao24, Guangyu Zhou24.
Data Coordination and Management Working Group
Lincoln D. Stein*1, Roderic Guigó82, Tim J. Hubbard22, Yann Joly26, Steven M. Jones65, Arek Kasprzyk1, Mark Lathrop64,92, Nuria López-Bigas84, B. F. Francis Ouellette1, Paul T. Spellman77, Jon W. Teague22, Gilles Thomas93,94, Alfonso Valencia90, Teruhiko Yoshida21.
Data Release, Data Tiers and Publications Working Group
Karen L. Kennedy*22, Myles Axton95, Stephanie O. M. Dyke22, P. Andrew Futreal22, Daniela S. Gerhard5, Chris Gunter96, Mark Guyer12, Thomas J. Hudson1,2, John D. McPherson1,68, Linda J. Miller97, Brad Ozenberger12, Kenna M. Shaw5.
Data Coordination Centre
Arek Kasprzyk*1, Lincoln D. Stein*1, Junjun Zhang1, Syed A. Haider98, Jianxin Wang1, Christina K. Yung1, Anthony Cross1, Yong Liang1, Saravanamuttu Gnaneshan1, Jonathan Guberman1, Jack Hsu1.
International Data Access Committee
Martin Bobrow*27, Don R. C. Chalmers99, Karl W. Hasel6, Yann Joly26, Terry S. H. Kaan100, Karen L. Kennedy22, Bartha M. Knoppers26, William W. Lowrance101, Tohru Masui16, Pilar Nicolás31, Emmanuelle Rial-Sebbag28, Laura Lyman Rodriguez12, Catherine Vergely102, Teruhiko Yoshida21.
Australia – Pancreatic Cancer (Ductal adenocarcinoma) and Ovarian Cancer (Serous adenocarcinoma)
Sean M. Grimmond*63, Andrew V. Biankin38,39, David D. L. Bowtell60,61, Nicole Cloonan63, Anna deFazio103,104, James R. Eshleman105, Dariush Etemadmoghadam60,61, Brooke A. Gardiner63, James G. Kench38,106, Aldo Scarpa53,54, Robert L. Sutherland38, Margaret A. Tempero107, Nicola J. Waddell63, Peter J. Wilson63.
Canada – Pancreatic Cancer (Ductal adenocarcinoma)
John D. McPherson*1,68, Steve Gallinger108,109, Ming-Sound Tsao110,111, Patricia A. Shaw112, Gloria M. Petersen113, Debabrata Mukhopadhyay114, Lynda Chin41,42, Ronald A. DePinho41,115, Sarah Thayer116, Lakshmi Muthuswamy1, Kamran Shazand1, Timothy Beck1, Michelle Sam1, Lee Timms1, Vanessa Ballin1.
China – Gastric Cancer (Intestinal- and diffuse-type)
Youyong Lu*18, Jiafu Ji18, Xiuqing Zhang24, Feng Chen18, Xueda Hu24, Guangyu Zhou24, Qi Yang24, Geng Tian24, Lianhai Zhang18, Xiaofang Xing18, Xianghong Li18, Zhenggang Zhu117, Yingyan Yu117, Jun Yu118, Huanming Yang24.
European Union/France – Renal Cancer (Renal cell carcinoma; focus on but not limited to clear cell subtype)
Mark Lathrop*64,92, Jörg Tost64,92, Paul Brennan119, Ivana Holcatova120, David Zaridze121, Alvis Brazma80, Lars Egevad122, Egor Prokhortchouk123, Rosamonde Elizabeth Banks124, Mathias Uhlén125, Anne Cambon-Thomsen28, Juris Viksna126, Fredrik Ponten127, Konstantin Skryabin128.
European Union/United Kingdom – Breast Cancer (Subtypes defined by an amplification of ER+ HER ductal-type)
Michael R. Stratton*22, P. Andrew Futreal22, Ewan Birney80, Ake Borg129, Anne-Lise Børresen-Dale130,131, Carlos Caldas132, John A. Foekens133, Sancha Martin22, Jorge S. Reis-Filho134, Andrea L. Richardson135,136, Christos Sotiriou137, Hendrik G. Stunnenberg70, Gilles Thomas93,94, Marc van de Vijver55,56, Laura van't Veer55.
France – Breast Cancer (Subtype defined by an amplification of the HER2 gene)
Fabien Calvo*9, Daniel Birnbaum40, Hélène Blanche92, Pascal Boucher9, Sandrine Boyault138, Christian Chabannon9,40, Ivo Gut64, Jocelyne D. Masson-Jacquemier40, Mark Lathrop64,92, Iris Pauporté9, Xavier Pivot139, Anne Vincent-Salomon140, Eric Tabone138, Charles Theillet141, Gilles Thomas93,94, Jörg Tost64,92, Isabelle Treilleux138.
France – Liver Cancer (Hepatocellular carcinoma; secondary to alcohol and adiposity)
Fabien Calvo*9, Paulette Bioulac-Sage142, Bruno Clément43, Thomas Decaens143,144, Françoise Degos45, Dominique Franco145, Ivo Gut64, Marta Gut92, Simon Heath64, Mark Lathrop64,92, Didier Samuel146,147, Gilles Thomas93,94, Jessica Zucman-Rossi148.
Germany – Pediatric Brain Tumors (Medulloblastoma, Pediatric Pilocytic Astrocytoma)
Peter Lichter*37, Roland Eils*37,149, Benedikt Brors37, Jan O. Korbel80,150, Andrey Korshunov151, Pablo Landgraf152, Hans Lehrach153, Stefan Pfister37,154, Bernhard Radlwimmer37, Guido Reifenberger155, Michael D. Taylor156,157, Christof von Kalle158,159.
India – Oral Cancer (Gingivobuccal)
Partha P. Majumder*67, Rajiv Sarin52, T. S. Rao8, M. K. Bhan8.
Italy – Rare Pancreatic Tumors (Enteropancreatic endocrine tumors and rare pancreatic exocrine tumors; intraductal papillary mucinous neoplasms, solid pseudopapillary tumors, mucinous cystic neoplasms and other rarer tumors)
Aldo Scarpa*53,54, Paolo Pederzoli160, Rita T. Lawlor54, Massimo Delledonne161, Alberto Bardelli162,163, Andrew V. Biankin38,39, Sean M. Grimmond63, Thomas Gress164, David Klimstra165, Giuseppe Zamboni53.
Japan – Liver Cancer (Hepatocellular carcinoma; virus associated)
Tatsuhiro Shibata*21, Yusuke Nakamura49,166, Hidewaki Nakagawa49, Jun Kusuda16, Tatsuhiko Tsunoda49, Satoru Miyano166, Hiroyuki Aburatani57, Kazuto Kato30, Akihiro Fujimoto49, Teruhiko Yoshida21.
Spain – Chronic Lymphocytic Leukemia (with mutated and unmutated IgVH)
Elias Campo*167, Carlos López-Otín66, Xavier Estivill58,59, Roderic Guigó82, Silvia de Sanjosé168, Miguel A. Piris51, Emili Montserrat167, Marcos González-Díaz44, Xose S. Puente66, Pedro Jares167, Alfonso Valencia90, Heinz Himmelbaue58, Victor Quesada66, Silvia Bea167.
United Kingdom – Breast Cancer (Triple Negative/lobular/other)
Michael R. Stratton22, P. Andrew Futreal22, Peter J. Campbell22,62, Anne Vincent-Salomon140, Andrea L. Richardson135,136, Jorge S. Reis-Filho134, Marc van de Vijver55,56, Gilles Thomas93,94, Jocelyne D. Masson-Jacquemier40, Samuel Aparicio169, Ake Borg129, Anne-Lise Børresen-Dale130,131, Carlos Caldas132, John A. Foekens133, Hendrik G. Stunnenberg70, Laura van't Veer55, Douglas F. Easton170, Paul T. Spellman77, Sancha Martin22.
United States – The Cancer Genome Atlas
The Cancer Genome Atlas Research Network.
Initial Scientific Planning Committee
Thomas J. Hudson*1,2, Lynda Chin*41,42, Bartha M. Knoppers*26, Eric S. Lander*81, Peter Lichter*37, Lincoln D. Stein*1, Michael R. Stratton*22, Warwick Anderson3, Anna D. Barker5, Cindy Bell6, Martin Bobrow27, Wylie Burke171, Francis S. Collins172, Carolyn C. Compton5, Ronald A. DePinho41,115, Douglas F. Easton170, P. Andrew Futreal22, Daniela S. Gerhard5, Anthony R. Green173, Mark Guyer12, Stanley R. Hamilton174, Tim J. Hubbard22, Olli P. Kallioniemi175, Karen L. Kennedy22, Timothy J. Ley72,176, Edison T. Liu69, Youyong Lu18, Partha Majumder67, Marco Marra65, Brad Ozenberger12, Jane Peterson12, Alan J. Schafer20, Paul T. Spellman77, Hendrik G. Stunnenberg70, Brandon J. Wainwright177, Richard K. Wilson72,73, Huanming Yang24.
Footnotes
1Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
2Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.
3National Health and Medical Research Council, Canberra, Australian Capital Territory 2601, Australia.
4Project Management Agency, German Aerospace Center (DLR), 53175 Bonn, Germany.
5National Cancer Institute, US National Institutes of Health, Bethesda, MD 20892, USA.
6Genome Canada, Ottawa, ON K2P 1P1, Canada.
7Secretariat of State for Research, Ministry of Science and Innovation, 28027 Madrid, Spain.
8Department of Biotechnology, Ministry of Science & Technology, Government of India, New Delhi, Delhi 110003, India.
9Institut National du Cancer, 92513 Boulogne-Billancourt, France.
10Genomics and Systems Biology Unit, Health Research Directorate, European Commission, B-1049 Brussels, Belgium.
11Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health, Bethesda, MD 20892, USA.
12National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD 20892, USA.
13Cancer Research UK, London WC2A 3PX, UK.
14Sidra Medical and Research Center, Qatar Foundation, Doha, Qatar.
15Department of Clinical Pharmacology, University of Oxford, Oxford OX2 6HE, UK.
16National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan.
17Division of Molecular Life Sciences, Federal Ministry of Education and Research, 11055 Berlin, Germany.
18Beijing Cancer Institute and Hospital, Peking University School of Oncology, 100142 Beijing, China.
19German Cancer Aid, 53113 Bonn, Germany.
20Wellcome Trust, London NW1 2BE, UK.
21National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
22Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
23Yokohama Institute, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
24BGI-Shenzhen, Shenzhen, 518083 Guangdong, China.
25The Hong Kong University of Science and Technology, Hong Kong, China.
26Centre of Genomics and Policy, McGill University and Génome Québec Innovation Centre, Montreal, QC H3A 1A4, Canada.
27Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
28U558, INSERM, 31073 Toulouse, France.
29University of North Carolina School of Pharmacy, Division of Pharmaceutical Outcomes and Policy, Institute for Pharmacogenomics and Individualized Therapy, Chapel Hill, NC 27599, USA.
30Institute for Research in Humanities, Graduate School of Biostudies, Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Kyoto 606-8501, Japan.
31Inter-University Chair in Law and the Human Genome, University of Deusto, Bilbao, 48007 Bizkaia, Spain.
32The Ethox Centre, University of Oxford, Oxford OX3 7LF, UK.
33Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
34Center for Human Genetics, University Hospitals Case Medical Center, Cleveland, OH 44106, USA.
35St John of God Pathology, Subiaco, Western Australia 6008, Australia.
36Schools of Surgery and Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
37German Cancer Research Center, 69120 Heidelberg, Germany.
38Garvan Institute of Medical Research, University of New South Wales, Darlinghurst, Sydney, New South Wales 2010, Australia.
39Department of Surgery, Bankstown Hospital, Bankstown, Sydney, New South Wales 2200, Australia.
40Institut Paoli-Calmettes, 13273 Marseille, France.
41Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
42Department of Dermatology, Harvard Medical School, Boston, MA 02115, USA.
43U991, INSERM, 35043 Rennes, France.
44Department of Hematology, Centro de Investigación del Cáncer, Hospital Universitario, Universidad de Salamanca, 37007 Salamanca, Spain.
45Hôpital Beaujon, 92110 Clichy, France.
46MLF Consulting, Arlington, MA 02474, USA.
47Canadian Tumour Repository Network, Winnipeg, MN R3M 0V5, Canada.
48Department of Internal Medicine, Division of Medical Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
49Center for Genomic Medicine, RIKEN, Yokohama, Kanagawa 230-0045, Japan.
50International Genomics Consortium, Phoenix, AZ 85004, USA.
51Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
52Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.
53Department of Pathology, University of Verona, 37134 Verona, Italy.
54Center for Applied Research on Cancer (ARC-NET), Verona University Hospital, 37134 Verona, Italy.
55Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
56Academic Medical Center, 1015 AZ Amsterdam, The Netherlands.
57Research Center for Advanced Science and Technology, University of Tokyo, Meguro-ku, Tokyo 153-8904, Japan.
58Center for Genomic Regulation, Pompeu Fabra University, 08003 Barcelona, Spain.
59Public Health and Epidemiology Network Biomedical Research Center (CIBERESP), Barcelona, 08003 Catalonia, Spain.
60Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.
61Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
62Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK.
63Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4067, Australia.
64CEA/DSV/IG-Centre National de Genotypage, 91057 Evry, France.
65Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
66Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
67National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India.
68Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada.
69Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore 138672, Singapore.
70Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, 6500 HB Nijmegen, The Netherlands.
71Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.
72The Genome Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
73Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63108, USA.
74Applied Genomics Center, Fok Ying Tung Graduate School, HKUST, Hong Kong, China.
75Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong, China.
76Cancer Institute, Zhejiang University, 310009 Hangzhou, China.
77Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94510, USA.
78Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
79Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
80European Molecular Biology Laboratory-European Bioinformatics Institute, Hinxton, Cambridge CB10 1SD, UK.
81Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
82Spanish National Bioinformatics Institute (INB) and Center for Genomic Regulation, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
83Howard Hughes Medical Institute and Center for Biomolecular Science and Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
84Research Unit on Biomedical Informatics, Department of Experimental and Health Science, Pompeu Fabra University, 08003 Barcelona, Spain.
85Department of Computer Science & Center for Computational Molecular Biology, Brown University, Providence, RI 02912, USA.
86Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
87Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
88Department of Statistics, University of California Berkeley, Berkeley, CA 94720, USA.
89Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
90Spanish National Bioinformatics Institute (INB) and Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
91Human Genome Sequencing Center & Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
92Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 75010 Paris, France.
93Université Claude Bernard Lyon 1, 69622 Villeurbanne, France.
94Fondation Synergie Lyon Cancer, 69008 Lyon, France.
95Nature Genetics, New York, NY 10013-1917, USA.
96HudsonAlpha Institute for Biotechnology, Huntsville, AL 35806, USA.
97Nature and the Nature research journals, New York, NY 10013, USA.
98Computer Laboratory, University of Cambridge, Cambridge CB3 0FD, UK.
99Faculty of Law, University of Tasmania, Hobart, Tasmania 7001, Australia.
100Faculty of Law, National University of Singapore, Singapore 259776, Singapore.
101Consultant in Health Research Ethics and Policy, 34280 La Grande Motte, France.
102ISIS 39 rue Camille Desmoulins, Institut Gustav Roussy, Pediatric Sce, 94805 Villejuif, France.
103Department of Gynaecological Oncology, Westmead Hospital, Westmead, Sydney, New South Wales 2145, Australia.
104Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Westmead, Sydney, New South Wales 2145, Australia.
105Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
106Department of Anatomical Pathology, Royal Prince Alfred Hospital, University of Sydney, Camperdown, Sydney, New South Wales 2050, Australia.
107Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA.
108Department of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada.
109Samuel Lunenfeld Research Institute, Toronto, ON M5S 1A1, Canada.
110Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2M9, Canada.
111Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A1, Canada.
112Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada.
113Department of Health Science Research, Mayo Clinic, Rochester, MN 55905, USA.
114Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
115Department of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, USA.
116Department of Surgery, Harvard Medical School, Boston, MA 02115, USA.
117Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
118Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
119International Agency for Research on Cancer, 69372 Lyon, France.
120Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, 121 08 Prague, Czech Republic.
121Department of Epidemiology and Prevention, N. N. Blokhin Russian Cancer Research Centre, Moscow 115478, Russian Federation.
122Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
123Bioengineering Center, Russian Academy of Sciences, Moscow 117312, Russian Federation.
124Cancer Research UK Centre, Leeds Institute for Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, UK.
125Science for Life Laboratory, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
126Institute of Mathematics and Computer Science, University of Latvia, Riga LV-1459, Latvia.
127Uppsala University, SE-751 05 Uppsala, Sweden.
128Kurchatov Scientific Center, Moscow 123182, Russian Federation.
129Department of Oncology, Lund University, SE-221 85 Lund, Sweden.
130Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, 0310 Oslo, Norway.
131Faculty of Medicine, University of Oslo, 0316 Oslo, Norway.
132Department Oncology, University of Cambridge and Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.
133Department of Medical Oncology, Erasmus MC Rotterdam, Josephine Nefkens Institute and Cancer Genomics Centre, 3015 CE Rotterdam, The Netherlands.
134Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London SW3 6JB, UK.
135Dana-Farber Cancer Institute, Boston, MA 02115, USA.
136Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
137Jules Bordet Institute, B-1000 Brussels, Belgium.
138Centre Léon Bérard, 69373 Lyon, France.
139Hôpital Jean Minjoz, 25030 Besançon, France.
140Institut Curie, 75231 Paris, France.
141Centre Val d'Aurelle Paul-Lamarque, 34298 Montpellier, France.
142Hôpital Pellegrin, 33076 Bordeaux, France.
143Hôpital Henri Mondor, 94010 Créteil, France.
144U955, INSERM, 94000 Créteil, France.
145Hôpital Antoine Béclère, 92141 Clamart, France.
146Centre Hepato-Bilaire, AP-HP Hôpital Paul-Brousse, 94800 Villejuif, France.
147U785, INSERM, 94800 Villejuif, France.
148U674, INSERM, 75010 Paris, France.
149BioQuant, Heidelberg University, 69120 Heidelberg, Germany.
150Genome Biology Unit, European Molecular Biology Laboratory, 69126 Heidelberg, Germany.
151Department of Neuropathology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
152Clinic for Pediatric Oncology, Hematology and Immunology, Heinrich-Heine University Hospital, 40225 Düsseldorf, Germany.
153Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
154Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
155Institute of Neuropathology, Heinrich-Heine University, 40001 Düsseldorf, Germany.
156Division of Neurosurgery, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
157Labatt Brain Tumor Research Center, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
158National Center for Tumor Diseases, 69120 Heidelberg, Germany.
159Division of Translational Oncology, German Cancer Research Center, 69120 Heidelberg, Germany.
160Department of Surgery, University Hospital Trust of Verona, 37134 Verona, Italy.
161Functional Genomics Center, Department of Biotechnology, University of Verona, 37134 Verona, Italy.
162Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, University of Torino, 10060 Torino, Italy.
163FIRC Institute of Molecular Oncology, 20139 Milan, Italy.
164Department of Gastroenterology, Endocrinology, Metabolism and Infectiology, University of Marburg, 35043 Marburg, Germany.
165Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
166Human Genome Center, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
167Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain.
168Unit of Infections and Cancer, Cancer Epidemiology Research Programme, CIBER Epidemiología y Salud Pública, Institut Català d'Oncologia-IDIBELL, 08907 Hospitalet de Llobregat, Spain.
169BC Cancer Research Centre, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
170Departments of Public Health and Primary Care and Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
171Department of Bioethics and Humanities, University of Washington, Seattle, WA 98195, USA.
172US National Institutes of Health, Bethesda, MD 20892, USA.
173Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Cambridge CB2 2XY, UK.
174Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
175Institute for Molecular Medicine Finland, University of Helsinki, FIN-00290 Helsinki, Finland.
176Departments of Medicine and Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
177Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.