International Cancer Genome Consortium
CancerA Disease of the Genome
Challenge in Treating Cancer:
Every tumor is different
Every cancer patient is different
Goals of Cancer Genome Research
Identify changes in the genomes of tumors that drive cancer progression
Identify new targets for therapy
Select drugs based on the genomics of the tumor
Systematic studies of cancer genomes
High rate of abnormalities> often 10,000 mutations per cancer
- minority are “driver” mutations- vast majority are “passengers”
Heterogeneity within and across tumor types
Sample quality matters
‘Next Generation’ sequencing instruments are providing new opportunities for comprehensive analyses of cancer genomes
Capacity of new instruments 100,000 to 1,000,000 times that of instruments used for Human Genome Project
Drastic decrease in costs per genome
Applications: DNA, RNA, chromatin (i.e. epigenome)
Sequencing Evolution/Revolution
1990: thousand bases/day
2000: million bases/day
2010: billion bases/day
International Cancer Genomics
Strategy MeetingOctober 1–2, 2007 Toronto (Canada)
22 countries represented120 participants 34 Genome or Cancer Center Directors
24 Representatives from funding agencies
62 Scientists selected to represent ethics, technologies, statistics, informatics, pathology, clinical oncology and cancer biology
Rationale for an International Consortium
• The scope is huge, such that no country can do it all.
• Coordinated cancer genome initiatives will reduce
duplication of effort for common tumors and ensure
complete studies for many less frequent forms of cancer.
• Standardization and uniform quality measures across
studies will enable the merging of datasets, increasing
power to detect additional targets.
• The spectrum of many cancers varies across the world
for many tumor types.
• The ICGC will accelerate the dissemination of genomic
and analytical methods across participating sites, and the
user community.
ICGC Goal
To obtain a comprehensive description of
genomic, transcriptomic and epigenomic
changes in 50 different tumor types and/or
subtypes which are of clinical and societal
importance across the globe.
- 500 tumors per tumor type
> 25,000 cancer genomes!
April 2010: World Map of Comprehensive Cancer Genome Projects
Commitments for > 10,000 tumor genomes!
New RFAs/projects in development
SELECTED FEATURES OF ICGC
(April 2010)
The level of organization is at the specific cancer type or subtype.
A particular cancer may be investigated by an individual research
lab/center or by a collaborative research group, across
jurisdictions.
The key to inclusion of a project in the ICGC is that it should take
a comprehensive, genome-wide approach to the analysis of that
tumor type (or sub-type).
The ICGC is open to many organizations willing mount a
comprehensive analysis of at least one cancer type or subtype,
and that agree to carry out their efforts according to ICGC
policies.
Basic Tenets
Organization
CLL
HCC
GBM
LungNSCLC
BreastHer+
Colon
etc.
Study Design and Statistical Issues
Every cancer genome project should state a clear rationale for its choice of sample size, in terms of the desired sensitivity to detect mutations. The target number is 500 samples per tumor type/subtype.
Fewer than 500 samples will be acceptable for rare and homogeneous tumors; more than 500 samples may be required for tumors that demonstrate considerable heterogeneity
Tumor Types and Subtypes
The ICGC aims to study cancers of all major organ systems
Studies will cover adult and childhood / adolescent cancers
Guidelines have been developed for ICGC participants for the selection of Cancer Genome Projects
Biobanking needs for ICGC and Cancer Research
This is HARD!
Sample collection can easily be rate limiting
Much of sample collection needs to be prospective
Quality assessment is critical
A committee of clinical and pathology experts (with representation from different institutions) is needed to draft and oversee the specific guidelines that will apply for every tumor type or sub-type.
All samples have to be reviewed by two or more reference pathologists.
Patient-matched control samples, representative for the germline genome, are mandatory to discern “somatic” from “inherited” mutations.
Clinical annotation of specimens are critical, ranging from exposures to outcomes
ICGC Consent and Privacy Protection Policies
ICGC membership implies compliance with Core Bioethical Elements for samples used in ICGC Cancer Projects ICGC acknowledges that the informed consent process used by ICGC members will necessarily differ according to local, socio-cultural and legal requirements
To minimize the risk of patient/individual identification, the ICGC has established the policy that datasets be organized into two categories, open and controlled-access.
Data Releases
ICGC Open Access Datasets
ICGC Controlled Access Datasets
Cancer PathologyHistologic type or subtypeHistologic nuclear grade
Patient/PersonGenderAge range
Gene Expression (normalized) DNA methylation Genotype frequencies Computed Copy Number and
Loss of Heterozygosity Newly discovered somatic
variants
Detailed Phenotype and Outcome Data
Patient demographyRisk factorsExaminationSurgery/Drugs/RadiationSample/SlideSpecific histological featuresProtocolAnalyte/Aliquot
Gene Expression (probe-level data)Raw genotype callsGene-sample identifier linksGenome sequence files
Genome Analyses
Mandatory: Genomic DNA analyses of tumors (and matching control DNA) are core elements of the project.
Complementary (Recommended): Additional studies of DNA methylation and RNA expression are recommended on the same samples that are used to find somatic mutations.
Optional: Proteomic analysesMetabolomic analysesImmunohistochemical analyses
Genome Analyses
Whole genome shotgun analyses (long-term goal)
Interim, large-scale, catalogues of somatic mutations– Sequencing of all coding exons and other genomic
regions of particular biological interest for point mutations.
– Analysis of low genome coverage of paired-end reads for rearrangements.
– Genotyping arrays, to detect copy number changes, LOH and breakpoint information.
Analyses of DNA Methylation
Expression Analyses: protein coding genes, non-coding RNAs, notably microRNAs.
ICGC Data Coordination Centre
Mission
• Establish common standards, data models,
reference datasets
• Develop and maintain ICGC web portal for
data dissemination
• Protect sensitive data
• Coordinate data releases
• Provide support and training
ICGC Database Model
Access mechanisms for Controlled Data
Data Access Compliance Office (DACO)
All ICGC members agree not to make claims to possible IP derived from primary data (including somatic mutations) and to not pursue IP protections that would prevent or block access to or use of any element of ICGC data or conclusions drawn directly from those data.
Note: Users of the data (including Consortium members) may elect to perform further research that would add intellectual and resource capital to ICGC data and elect to exercise their IP rights on these downstream discoveries. However, ICGC participants and other data users are expected to implement licensing policies that do not obstruct further research: (http://tinyurl.com/4rslvy).
ICGC Intellectual Property Policy
ICGC Data Release Policies
The members of the International Cancer Genome Consortium (ICGC) are committed to the principle of rapid data release to the scientific community.
The individual research groups in the ICGC are free to publish the results of their own efforts in independent publications at any time.
Data Release, Data Tiers & Publications Working Group
Data users are free to use data that targets specific genes & mutations without any restrictions.
ICGC member projects may, if they choose, impose a publication moratorium period that will only limit other data users from publishing global analyses. All data shall become free of a Publication Moratorium when either the data are published by the ICGC member project or 1 year after the specified quantity of data on which the initial global analyses will be carried out (e.g. genome dataset from 100 tumors per project) have been released via the ICGC portal or other public databases.
In all cases data shall be free of any restriction 2 years after its initial release.
ICGC Data Generation has started
(April 2010)
http://icgc.org
“OPEN” ICGC Data sets in DCCApril 2010
Institute Tumour type # Donor # Samples
OICR, Canada pancreas 2 6• 2 primary• 2 cell line • 2 xenograft
Garvan, Australia
pancreas 4 6• 1 primary• 4 cell line • 1 control
Japan liver 2 2 primary
Sanger skin 1 1 cell line
Sanger lung 1 1 cell line
Sanger breast 24 24• 15 primary• 9 cell line
Institute Tumour type # Donor # Samples
TCGA, USA GBM 380 687 - multiple use of same sample
• 317 control• 378 primary
ovarian 386 764 - multiple use of same sample
• 386 control• 379 primary
Hopkins, USA GBM 105 • 37 primary• 68 xenograft
pancreas 114 • 97 xenograft• 17 cell line
breast 48 • 36 xenograft• 12 cell line
colorectal 37 • 30 xenograft• 7 cell line
Additional “OPEN” Data sets in DCC, April 2010
Reference cancer genome used by ICGC to compare methods is
available via DCC
COLO-829 malignant melanoma cell line
ICGC Marker Paper
Nature 464, 993-998 (15 April 2010)
The International Cancer Genome Consortium can be the hub of the wheel, but it’s not all of cancer research!
Translating into new interventions, tests, and public health strategies will require biological and clinical studies, changes in health care practices, and
TIME!
2007
2008
2009
2010
Funding/Projects
Data Management
Ethics
Samples
Data Analysis
Data AccessData
An Idea
Discussions
The Launch
A Plan
A Working Consortium
A Consortium sharing ideas and expertise
A Consortium coordinating and collaborating
The Consortium The Work
Pathology
Rare/ChildhoodCancers
3-4 more…
1 project
8 projects
10 projects
3rd Workshop of the International Cancer Genome
Consortium (ICGC)Madrid, Spain – March 2010