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NCI Tumor Signatures Meeting - Executive Summary

On October 11 and 12, 2018, the National Cancer Institute (NCI) convened a group of experts to discuss the current state of the science of mutational signatures in cancer research and related opportunities and challenges. The goals of the meeting were to:

  • Identify major issues and future directions in the characterization of mutational signatures that could lead to new insights into etiology, outcomes, and risk factors for specific cancers.
  • Encourage discussion to inform NCI priorities and frame critical research questions.
  • Develop new collaborations to advance research on mutational signatures and their application in clinical practice.

Next steps to be considered by the NCI include the following: 

  • Increase integration with the field of cancer biology, including developing larger data sets and collaborations with basic scientists. NCI is developing an organoid library that might be useful to test exposures to different chemicals following exposure over time.
  • Evaluate current algorithms used to benchmark mutational signatures in coordinated competition open to entire community.
  • Determine the relative importance of coverage of the cancer genome (targeted vs. whole genome) for signature discovery and assessment, especially in clinical settings. Pursue the question of how deep coverage should be through a separate NCI-supported competition.
  • Determine how to assess and use Formalin-Fixed Paraffin-Embedded (FFPE) tissue samples.
  • Increase the depth of understanding of somatic signatures through integration with the genomic landscape, examining mistakes/mis-repairs and the role of germline mutations.
  • Determine the degree of precision for detecting signatures with respect to exposure/prognosis, beginning with known carcinogens.
  • Investigate the possible importance of tumor signatures by disparities, especially geographic and environmental differences as well as migration differentials.
  • Develop consensus on use of clinical signatures.
  • Support studies to address reverse assessments to identify promising therapies or germline/environmental triggers.

See participant list

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