Notice Number: NOT-CA-06-002

Key Dates
Release Date: November 9, 2005

Issued by
National Cancer Institute (NCI), (http://www.nci.nih.gov)

NIH is seeking input from the community.

This Request for Information (RFI) is for analysis and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Government. The Government does not intend to award a cooperative agreement, contract, or grant on the basis of responses to this RFI or otherwise pay for the preparation of any information submitted or for the Government's use of such information.

Background:

Cancer, with some exceptions, is a complex genetic disease in which mutations may contribute to its initiation and progression. Research has already identified a large number of mutations implicated in carcinogenesis, which has led to an understanding of many details underlying tumor development and progression. The successes of some newly introduced cancer drugs that act on known mutated proteins demonstrate that products of somatic genetic alterations are legitimate targets for therapy. However, given cancer's complexity, it is generally assumed that only a fraction of the molecular targets involved in carcinogenesis have been identified to date.

The complexity of cancer is perhaps best exemplified by the fact that there are many different human tumor types, each with distinct subgroups, and each presenting radically different scientific and clinical challenges. This heterogeneity arises, in part, from the fact that cancer genomes are dynamic and tumors are complex systems that are shaped by chromosome aberrations, nucleotide mutations, epigenetic phenomena, the cellular and biological context of the specific cancer, characteristics specific to the individual patient, and environmental influences. While certain similarities exist across cancer types, any effort to characterize the genomes of cancers in a comprehensive, systematic manner must address important questions related to heterogeneity.

In February 2005, the Directors of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) agreed to explore pursuing a 3-year pilot project, based on a recommendation in a recent National Cancer Advisory Board Biomedical Technology Subgroup Report (available at www.cancer.gov), to determine the feasibility of cataloging the genetic aberrations associated with a set of human cancers. Since cancer is a genetic disorder, in principle it should be possible to derive a complete catalog of mutations, and in some cases to determine other abnormalities. Once the information is known, a complete understanding of the functional consequences of these alterations can be used to develop and implement preventative or interventional strategies to eliminate and/or control cancer.

Information requested:

A comprehensive definition of molecular taxonomy for cancer is an ambitious endeavor. One of the important initial challenges is to identify which cancer(s) to study in the pilot project that will optimize the chance for initial success. Any investigator with biospecimen collections within the United States , or internationally, is encouraged to respond to the RFI and provide the information requested below. Please note that it would be very desirable if respondents provide a separate response for each significantly different cancer biorepository that they maintain.

With regard to any clinical protocols that were/are used, respondents should indicate whether or not the collection of biospecimens was or is being carried out in the context of a clinical trial. If clinical trials were or are involved, please indicate whether or not:

• a single specific disease stage was or is one of the selection criteria;
• surgical treatments in each arm of the trial were/are identical;
• the samples and data were or are collected as part of a “linked” or “coded” protocol (meaning that the patients can be anonymously tracked for the purpose of attaching longitudinal and outcomes data to the samples in accordance with adherence to Federal patient privacy regulations and protections);
• the length of follow-up was or is greater than 5 years; and
• the current status of the protocol (active or inactive).

Further, with regard to any clinical protocols that might have been or are still being followed, respondents should, if possible, indicate whether or not:

• the patients were or are consented broadly or narrowly (i.e., specifically) for certain genetic analyses of the cancer and control samples;
• DNA sequencing was or is specifically permitted;
• the patients can be re-contacted for additional consent; and
• re-contact for additional consent from patients was or is specifically permitted in the original consent or it was/is accomplished via an institutional review board (IRB) waiver.

With regard to any annotation of biospecimens, respondents should, if possible, indicate whether or not:

• the biospecimen annotation included or includes demographic, clinical, and pathologic data;
• the data existed or exists in electronic format; and
• “electronic” data included or includes images of paper records.

With regard to the contents of each biorepository , respondents should provide, if possible, the following details:

• numbers of patients (unique cases) included in the collection;
• anatomic sites and histopathologic types (WHO classification) represented in the collection (e.g., lung and squamous cell carcinoma, respectively);
• numbers of tumors by grade found within each histologic type; and
• proportions of the specimens that represented or represent metastatic disease (and numbers of positive lymph nodes associated with each case, if available).

Further, with regard to the contents of each biorepository , respondents should, if possible, describe:

• the percentage of biospecimens that were or are > 200 mg in weight;
• the percentage of the biospecimens that were or are of unknown weight;
• the method of storage of the biospecimens that was or is used (e.g., fresh frozen, embedded in OCT, formalin-fixed and paraffin-embedded, and/or combinations thereof); and
• the existence and characteristics of any case-matched normal tissue biospecimens.

With regard to standard operating, quality control, and quality assurance procedures , respondents should, if possible, indicate whether or not:

• the time from cut-off of blood supply to stabilization (i.e., warm ischemia time) was or is collected as a data element for each specimen;
• the cellular composition of each sample was or is known;
• the fraction of biospecimens that were or are greater than 80 percent tumor;
• each biospecimen was or is subjected to the quality control processes, including:
  • individual pathology verification;
  • capture and storage of digital images;
  • molecular analyte testing (e.g., gel-based RNA degradation testing, 18S/28S rRNA ratios, etc.); and
• biospecimens in the collection would or could be available for the use in a Federally-supported Human Cancer Genome Project if determined to be suitable for its pilot phase of study.

The goal of this RFI is to identify and gather data about the characteristics of existing human tumor repositories. The information gathered from this process will help distinguish the key features of biospecimen collections that could meet the needs of the pilot cancer genome characterization project. The NCI welcomes any additional information the respondent wishes to submit, such as details of repository contents, collection procedures, biorepository management procedures, and human subjects protocols. Please attach such information as appendices to the main response.

Responses:

The document should not be longer than five pages. It would be helpful if the data are provided in a tabular form. To assist you, we have provided two options for providing information directly through the CGAP web site ( cgap.nci.nih.gov) . The response deadline is 8 weeks from the publication of this announcement; therefore, the closing date is January 12, 2006 . If you choose to not fill out the form on the CGAP web site, please submit your responses to us either via mail or e-mail using the addresses shown below:

Daniela S. Gerhard, Ph.D.
Director
Office of Cancer Genomics
National Cancer Institute
31 Center Drive , Room 31A07
Bethesda , MD 20892
Telephone: 301-451-8027
Email: gerhardd@mail.nih.gov

Or

Cyndy Izadi
Administrative Program Assistant
Telephone: 301-451-8027
Fax: 301-480-4368
Email: izadic@mail.nih.gov

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