# Presentation: 948330

## Status Report: The Cancer Genome Atlas Pilot Project

**National Cancer Advisory Board Meeting**
- September 6, 2006
- Anna D. Barker, Ph.D.
- Deputy Director, National Cancer Institute

## TCGA:  An NCI – NHGRI Collaboration in Medical Genomics 

**The Cancer Genome Atlas (TCGA)**** ****is a 3-year pilot project of the ****National Cancer Institute and ****the National Human Genome Research Institute ****to increase our comprehensive understanding of the **_**genetic basis of cancer **_** **

**-**** ****It is anticipated that TCGA’s integrated database of molecular and clinical information will provide scientists unprecedented opportunities to discover and develop a new generation of targeted diagnostics, therapies and preventives for cancer -**** **

## Achievements
Human Genome Project
Gene families and pathways
Robust genomic analysis technologies
Sanger experience - sequenced known genes (e.g., kinases are druggable)
Number of early indications that somatic mutations are important potential targets

- Human Genome Project
- Gene families and pathways
- Robust genomic analysis technologies
- Sanger experience - sequenced known genes (e.g., kinases are druggable)
- Number of early indications that somatic mutations are important potential targets

_**Overall Impact**_
- Known human sequence
- Kinases, phosphatases, transcription factors, hormone responsiveness
- Copy number changes, expression profiling, potentially epigenomic technologies
- Survey of known genes that are abnormal *prior to sequencing - BRAF*
*BCR-ABL, EGFR1, ERBB2*

**Enabling Rationale for TCGA**

## TCGA Development Milestones

**TCGA Development Milestones**

**2003**

**2005**

**2004**

***September 2003:****  *NCAB Ad hoc Committee formed

***April 2004:**** *NCI-NHGRI Workshop

***January 2005:**** *Project RFI issued

***September 2004:****  *Presentation to EC

***November 2004:***  Presentation to BSA

***July 2005:****  *Meeting for community input

***November 2005:***
- Presentation to  the BSA  Approval
- NCI Issuance of Human Cancer Biospecimen RFI

***February 2005:****  *
- Ad hoc Committee Report to NCAB
- NCI-NHGRI Working Group formed

***December 2005:***
- NHGRI Issuance of Sequencing Centers RFA
- Public Launch of Pilot Project

***September 2005:***
- NCAB Review
- EC Review

## Project Development Milestones

**Project Development Milestones**

**Fiscal Year 2006**

***December 2006:  ***NHGRI Funding of High-throughput Sequencing Centers

**2006**

***March 2006:***
- NCI Issuance of Cancer Genome Characterization Centers RFA

***September/October 2006:****  *
- Selection of tumor types
- NCI Funding of Biospecimen Core Resource
- NCI Funding of Cancer Genome Characterization Centers

***May 2006:***
- Data Release Workshop

***July/August 2006:****  *
- Site visits to Biorepositories

***February 2006:***
- NCI Issuance of Biospecimen Core Resource RFP

## The Various Components of TCGA – Procurement Processes Ongoing 

**A patient donates tumor tissue for study.**

**Genome Sequencing Centers**

**Cancer Genome Characterization Centers**

**Data Management, Bioinformatics, and Computational Analysis**

**Human Cancer****Biospecimen Core Resource**

**Scientists analyze****the data produced by TCGA, and develop a web-based information database.**

**Scientists use information in the database to speed research advances.**

**Research results are translated into new products to help patients.**

**Scientists study genetic material in the tumor tissue.**

**To find the genetic signatures for cancer, scientists study genetic material in many patients’ tissues.  **

**Technology****Development**

**4**

## Upcoming Milestones for TCGA

- Finalize selection and award the Biospecimen Core Resource (Scheduled for September 13, 2006)
- Select the tumors to be used in TCGA Pilot (Single and/or multiple biospecimen collections) (Scheduled for September 13, 2006)
- Finalize selection and award the Genome Characterization Centers (October, 2006)
- Finalize selection and award bioinformatics support activities (October, 2006)
- Finalize selection and award Genome Sequencing Centers (NHGRI, December, 2006)
- Project launch – January, 2006

## Central to the Success of TCGA Pilot, the BCR will:
Verify all biologic and clinical data and perform the pathologic QC of qualified tumors from selected existing collections 
Perform central processing of specimens to provide uniform biomolecules and distribute to both genome characterization and sequencing centers 
Track and quality assure all specimen-related operations (consent, acquisition, transport, processing, QC, distribution) 
Provide “standard” samples for technology platform comparisons 
Develop (with the Office of Biorepositories and Biospecimens Research) and monitor the SOPs for prospective specimen collection
Serve as a member of TCGA’s Steering Committee
(Selected organization to support BCR will be named in Mid-September)

- Verify all biologic and clinical data and perform the pathologic QC of qualified tumors from selected existing collections
- Perform central processing of specimens to provide uniform biomolecules and distribute to both genome characterization and sequencing centers
- Track and quality assure all specimen-related operations (consent, acquisition, transport, processing, QC, distribution)
- Provide “standard” samples for technology platform comparisons
- Develop (with the Office of Biorepositories and Biospecimens Research) and monitor the SOPs for prospective specimen collection
- Serve as a member of TCGA’s Steering Committee
- (Selected organization to support BCR will be named in Mid-September)

**TCGA Biospecimen ****Core Resource (BCR) Functions**

## Categories of Biospecimen Collections (Tumor Types)  for TCGA

**To initiate TCGA one tumor type will be selected from qualifying biorepositories in **_**three categories**_**:  a tumor representing a major public health impact; a second tumor type that demonstrates a high degree of homogeneity; and the third, a tumor collection that derives from a completed clinical trial **

## Evaluation Process

2005 - A request for information (RFI) and notification to cancer centers
Biorepositories identified from RFI that met rigorous criteria (quality of samples, pathology, clinical and biologic data) and achieved ethical and legal specification were then screened using a series of primary criteria 
Qualifying collections were further evaluated using secondary criteria – and biorepositories were site-visited
Factors such as timing, logistics of collections and informed consent were factored in at this stage and a ranking in the three categories was developed
Qualifying biorepositories were further reviewed with input from an expert technical panel – composed of representatives from the surgery, pathology, scientist, patient advocate and bio-ethicist communities

**2005 - A request for information (RFI) and notification to cancer centers**
**Biorepositories identified from RFI that met rigorous criteria (quality of samples, pathology, clinical and biologic data) and achieved ethical and legal specification were then screened using a series of primary criteria **
**Qualifying collections were further evaluated using secondary criteria – and biorepositories were site-visited**
**Factors such as timing, logistics of collections and informed consent were factored in at this stage and a ranking in the three categories was developed**
**Qualifying biorepositories were further reviewed with input from an expert technical panel – composed of representatives from the surgery, pathology, scientist, patient advocate and bio-ethicist communities**

**Biospecimen Selection Process:**

## Biospecimen Collections Selection Criteria

_**Primary Criteria **__(Must meet all primary qualification criteria)__ _
- At least 250 samples of the same cancer type (combining samples from same cancer type may be pursued to insure statistical validity)
- Each cancer sample must be accompanied by samples of  matched “normal” tissue, such as blood, from the same patient
- Must be from clinical trial or similar study
- A minimum of 0.2 grams of tissue
- Patients gave permission to be re-consented

_**Secondary Criteria**_** **(Collections that met primary criteria were ranked for the following)
- Quality-control analyses of tissue sample     and biomolecules
- Sample characteristics
- Sample collection procedures and storage
- Clinical trial protocol and donor enrollment
- Informed consent
- Clinical data quality
- Clinical data electronic status
- Institution’s contractual capabilities

- Telephone Interviews were followed up with site visits by an NCI-NHGRI team

## Technology platforms for high throughput genome characterization 
Expression profiling
Copy number changes
DNA methylation (epigenomics)
Improve existing technologies
Epigenomics to meet required throughput rate
Copy number detection and expression profiling for characterizing small amount of biological samples
Real-time data release into public database
CGCCs RFA: 
U24 (cooperative agreement)
$11.7 million 
Peer Review: August 8-9, 2006
Awards to be announced: October 2006

**Expression profiling**
**Copy number changes**
**DNA methylation (epigenomics)**
**Improve existing technologies**
**Epigenomics to meet required throughput rate**
**Copy number detection and expression profiling for characterizing small amount of biological samples**
**Real-time data release into public database**
**CGCCs RFA:**
**U24 (cooperative agreement)**
**$11.7 million **
**Peer Review: August 8-9, 2006**
**Awards to be announced: October 2006**

**Cancer Genome ****Characterization Centers (CGCCs)**

## High-throughput Genome Sequencing Centers (NHGRI)
Sequence large number of targets from three tumor types
Develop and integrate sequencing technologies

Genome Sequencing Centers RFA: 
Mechanism:  U54 (cooperative agreement)
$50 million in sequencing for TCGA
Peer Review: July 13, 2006
Awards to be announced: December 2006

**Sequence large number of targets from three tumor types**
**Develop and integrate sequencing technologies**
**Genome Sequencing Centers RFA: **
**Mechanism:  U54 (cooperative agreement)**
**$50 million in sequencing for TCGA**
**Peer Review: July 13, 2006**
**Awards to be announced: December 2006**

**Genome Sequencing Centers**

## caBIG Will Provide a BioinformaticsPlatform for TCGA

**Clinical Data**

**Molecular Data**

**Data from Genome Characterization and Sequencing Centers **

**caBIG Will Provide a Bioinformatics****Platform for TCGA**

**NCI’s Cancer Bioinformatics Grid (caBIG):  Principal **
**Bioinformatics Resource for the Development of a Public TCGA Database**

## Ethical, Legal, and Policy Considerations 

**TCGA (and other large scale medical genomics efforts) must address several ethical, legal, and policy issues/questions:**
- How detailed should informed consent be – more information vs. less?
- Who should have access to data?
- How do we leverage and capitalize on potential for progress against disease and ensure privacy protection?
- Will we need new forums of patients, clinicians, researchers, ethicists to discuss these issues and inform policy?

**Notes:**
Return of Study Results:
Unclear what clinically relevant genetic/genomic information may be discovered (we don’t know what we don’t know...)
Develop policies and procedures for the return of results
Participate in identifying a system of care to provide genetic information/counseling to those research participants who have genetic concerns identified and no access to care

Data Release/IP Issues:
ELP group expect to participate in discussions with scientists and policy makers
Public release of sequence data
Release of health information with IRB approved protocols
Assist in the development of policies and procedures to protect participants’ privacy

## Ethical, Legal, and Policy Considerations (continued)

_**Informed Consent Issues**_
**Permission for detailed genomic research**
**Permission for broad future research use of samples and health information**
**Permission to place genomic & health information in widely-accessible databases**
**Risks associated with loss of privacy**
**Potential benefits for future cancer patients**
**Problems related to withdrawal**

**Notes:**
Consent Issues:

Suggested language for model consent is under IRB review (Both NCI and external IRBs)

## Some Expectations for TCGA - The Pilot Project

**Three-Year Horizon**
- Completion of genomic analysis of three tumors
- Ability to identify specific alterations in genes associated with cancer
- Ability to differentiate tumor subtypes based on genomic alterations
- Establishment of a database with all data from TCGA Pilot Project that scientists can access for follow-up experiments

## 
Identification of somatic changes in cancer genomes that could establish the molecular basis for each cancer – and inform and enable a new era of molecular oncology
A molecular taxonomy of cancer
New molecular targets for diagnostics, therapeutics and preventives
Improved ability to stratify patients for clinical trials

- Identification of somatic changes in cancer genomes that could establish the molecular basis for each cancer – and inform and enable a new era of molecular oncology
- A molecular taxonomy of cancer
- New molecular targets for diagnostics, therapeutics and preventives
- Improved ability to stratify patients for clinical trials

**TCGA’s Long View **

## For More Information: Joint NCI-NHGRI TCGA Website 

**Updates on ****TCGA website:**
- Information for patients, scientists, clinicians, policymakers, and the public
**Coming Soon:**Sign up at the TCGA website to receive automatic updates and event news

**http://cancergenome.nih.gov**

## The Future:  Personalized Cancer Medicine

- Image courtesy of *Science*, May 26, 2006

**The Future:  Personalized Cancer Medicine**