U24CA258115

Genomic Expert Curation Panels for Pediatric Malignancies - Project Summary/Abstract

The goal of this proposal is to develop expert panels focused on curating evidence for the clinical application of somatic mutations associated with childhood cancers. Tumors in the pediatric population have unique genetic profiles that can affect their diagnosis, prognosis, and treatment. Currently, there is a gap in the representation of somatic variants for childhood tumors in public cancer databases and knowledge bases. New approaches for evidence curation are needed to identify important mutations in childhood cancers for both diagnosis and therapy response.

To address these gaps, our application builds on two prominent developments in the field led by our team. First, as the ClinGen Somatic Clinical Domain Working Group (CDWG), we developed the Minimal Variant Level Data (MVLD) standard to promote sharing and use of gene variants in precision oncology. Second, we developed the Clinical Interpretation of Variants in Cancer (CIVIC) expert crowdsourced platform for somatic curation and clinical interpretation.

Our goals are to:

1. Systematically catalog the clinical relevance of common, rare, and novel variants identified through gene-specific and genome-scale testing in childhood cancers.
2. Partner with ClinGen, ClinVar, guideline-setting professional organizations, and other relevant global efforts to translate and present the knowledge derived from genome researchers and clinical laboratories.
3. Develop informatics support for variant assessment of clinical actionability, information display, interfacing with relevant databases, and dissemination.

To accomplish these goals, we developed a collaboration over the past three years through the ClinGen Somatic CDWG among researchers at Washington University, Georgetown University, and Children's Hospital Los Angeles. This collaboration includes clinical and molecular geneticists, genetic counselors, bioinformaticians, and genomic database experts to advance the use of genomic data in childhood cancers.

Specifically, we will establish pilot Variant Curation Expert Panels (VCEPs) to assess the clinical relevance and actionability of somatic variants in pediatric cancers. Our initial focus will be on two disease areas, with timely relevance: pediatric malignancies with NTRK fusions and BCR-ABL1 (Philadelphia)-like B-lymphoblastic leukemia (PH-Like B-ALL). We will adopt ClinGen's existing VCEP policies and processes for assessing variants of strong clinical significance, potential clinical significance, unknown clinical significance, and benign or likely benign variants in childhood cancers. We will adapt and enhance the CIVIC platform to support these expert panels. The CIVIC platform will also provide the curated evidence in standard formats for the exchange of data with ClinVar and ClinGen resources.

Finally, we will seek FDA recognition for the evidence repository developed and curated through this grant.

Washington University

TO IMPROVE SCREENING AND EARLY DETECTION STRATEGIES AND TO DEVELOP ACCURATE DIAGNOSTIC TECHNIQUES AND METHODS FOR PREDICTING THE COURSE OF DISEASE IN CANCER PATIENTS. SCREENING AND EARLY DETECTION RESEARCH INCLUDES DEVELOPMENT OF STRATEGIES TO DECREASE CANCER MORTALITY BY FINDING TUMORS EARLY WHEN THEY ARE MORE AMENABLE TO TREATMENT. DIAGNOSIS RESEARCH FOCUSES ON METHODS TO DETERMINE THE PRESENCE OF A SPECIFIC TYPE OF CANCER, TO PREDICT ITS COURSE AND RESPONSE TO THERAPY, BOTH A PARTICULAR THERAPY OR A CLASS OF AGENTS, AND TO MONITOR THE EFFECT OF THE THERAPY AND THE APPEARANCE OF DISEASE RECURRENCE. THESE METHODS INCLUDE DIAGNOSTIC IMAGING AND DIRECT ANALYSES OF SPECIMENS FROM TUMOR OR OTHER TISSUES. SUPPORT IS ALSO PROVIDED FOR ESTABLISHING AND MAINTAINING RESOURCES OF HUMAN TISSUE TO FACILITATE RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.394 - Cancer Detection and Diagnosis Research

National Cancer Institute (NCI) [HHS - NIH]

Missouri United States

State-Wide

Genomic Expert Curation Panels (U24 Clinical Trial Not Allowed) (PAR-20-101)

Amendment Since initial award the total obligations have increased 173% from $318,793 to $870,157.