Recommendations: Balancing the portfolio of phenotypes for gene discovery using linkage analysis

• Undertake targeted efforts to increase linkage investigation of under-represented sites: germ cell, brain, leukemia, lymphoma, pancreas, biliary, multiple cancers.

• Strengthen the portfolio through expanded investigations of other types of families: high aggregation multi generational families (additional common as well as rare cancer types), families with known "positive" mutation status, affected relative sets, cancer families with cancer-related phenotypes (e.g., penetrance, age-of-onset, other).

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Recommendations: Connecting families to researchers

• Standardize the collection of family history to obtain appropriate information that would lead to identification of potential cancer families, noting the need for careful consideration of the separation of clinical care vs. research records since the two different types of records have very different privacy/confidentiality protections, and the need to develop instruments that are user- friendly (i.e., useable by community-based physicians).

  Develop and pilot a standardized family history instrument, models of informed consent, and data management tools

  Work with Cancer Centers to make standardized family history taking a standard of care, and to develop a template for it

• Develop and provide mechanisms to facilitate self-referral by individuals and families; coordinate efforts with professional societies to encourage physicians to refer families. Explore opportunities available through patient advocacy groups, CIS, etc.; consider developing "swat teams", utilizing contracts, etc. A public awareness campaign focused on the search for cancer genes could be an effective strategy for encouraging individuals and families to come forward.

• Facilitate the formation of investigator-initiated consortia/teams focused on the genetics of different types of cancers to foster collaborative efforts (i.e., under represented sites-see first bulleted action item). Develop flexible funding mechanisms to support this effort; i.e., support for workshops focused on the genetics of different types of cancer or collaborative projects. Address the need for an appropriate academic reward system for collaborative researchers. Develop a mechanism for interaction/communication among and between these groups (i.e., an electronic newsgroup).

• Develop mechanisms to systematically identify and distribute information on all of the NCI/NIH-supported individuals/groups studying families. Develop mechanisms to encourage open access to these resources. There is a need to raise the level of awareness on the availability and on how to access NCI supported resources. A user-friendly web-enabled directory or catalogue of "all" existing NCI-supported resources (i.e., SEER, CFR, specimen resources) would greatly benefit the extramural scientific community.

• Organize a workshop to explore the utility and practical research considerations (strategies for the identification, characterization, etc.) for working with special and isolated populations with small founder pools.

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Recommendations: Genetically characterizing families

• Support extended characterization of cancer-gene positive families, families tested for known cancer genes who are negative for those genes, and families with cancer-relevant phenotypes

• Expand NCI utilization of CIDR for genotyping cancer families. Provide investigators who have collected DNA samples on large pedigrees with resources for whole genome scanning; provide investigators who have identified probands with known mutation status with the resources to extensively characterize probands'families.

• Link genotyping technology developers with researchers who will be using the technology.Develop technology to reduce the unit cost of high throughput sequencing and genotyping. Establish criteria for acceptable levels of sensitivity and specificity ("good enough" criteria) for research quality genotyping /mutation characterization.

• Support development of methods to perform genotyping on very small amounts of DNA

• Support the development of non-invasive technology to obtain DNA samples

• Develop a cost-effective, centralized mechanism for doing fine structure mapping; it may be appropriate to consider expanding the capabilities of CIDR to include fine structure mapping

Recommendations: Informatics Support of the Linkage Paradigm

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• Develop/use common analysis tools and platforms (such as Linkage package, Gene Hunter, SAGE package)

• Assess informatics tools/systems being utilized in NCI supported activities (e g. the Cancer Genetics Network).

• Develop tools to assess the quality of genotype information.

• Develop improved tools to manage family data. This may be a "by-product" of the development of a standardized family history instrument

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