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Childhood cancers present numerous challenges for variant interpretation in a clinical context due to their rarity, low mutation burden, and diversity of unique molecular alterations, many of which are not found in adult cancers. Consequently, variants associated with childhood tumors are under-represented in public cancer databases. Thus, a focused and directed effort is needed for the structured curation of genetic variant data to document diagnostic, prognostic, therapeutic, and hereditary-risk variants for childhood cancers. The ClinGen Somatic Pediatric Cancer Taskforce (PCT) seeks to address these challenges through multiple initiatives. By extensively analyzing the WHO Classification of Tumours Online: Paediatric Tumours volume and reviewing NCCN Guidelines, the PCT created a master list of key genomic alterations (n=975) in pediatric brain, solid, or hematologic malignancies (>180 ICD-O-3.2 diagnoses) that are drivers or have clinical impact to prioritize genes for curation in the CIViC (civicdb.org) knowledgebase. The PCT developed a pediatric specific curation Standard Operating Procedure for the entry of evidence into CIViC to instruct curators on how to tag pediatric evidence based on age of onset and the selection of the most appropriate ICD-O-3.2 disease. In collaboration with the Human Disease Ontology (DO; disease-ontology.org), 464 hematologic and brain cancer ICD-O-3.2 terms have been added to the DO to aid curated disease selection. To aid curators, the natural language processing methods of CIViCmine (bionlp.bcgsc.ca/civicmine) have been adapted to better recognize publications with pediatric evidence. Our efforts support the public dissemination of high-quality childhood cancer focused variant interpretations in the CIViC knowledgebase. [ABSTRACT FROM AUTHOR]

The Sarcoma Working Group of the Cancer Genomics Consortium (CGC) aims to understand the current state of diagnostic testing for pediatric sarcomas and the challenges faced in the field. We conducted a survey of CGC general constituents and American Cytogenetics Forum members (CYTOGN-L@LISTSERV.SC.EDU) in April/May 2022. In total, 46 responses were received, predominantly from university/academic/teaching hospitals (n=45) in the United States (n=41) and Canada (n=5). Respondents reported diverse roles including laboratory directors (n=25), pathologists (n=15), oncologists (n=3), and laboratory technologists (n=3). While most participants reported having in-house FISH (n=40) and/or conventional karyotyping (n=28) assays available for pediatric sarcomas, less than 40% of laboratories offer microarray and/or comprehensive NGS testing clinically. Detailed information on methodology and reported variant types will be discussed. When asked about genetic testing conundrums faced in their practice, the most common response was the scarcity of testing algorithm guidelines (n=12). Additional recurring challenges included: lack of support for new test development and issues with sendout testing (n=6), insufficient knowledge to interpret and act on results (n=4) or when to perform germline testing (n=3), limited tissue for comprehensive testing (n=3), and insurance/reimbursement complications (n=3). To address gaps in guidance for testing, the Workgroup is preparing a manuscript that will report survey results, provide practical scenario-based examples informed by the survey results and supported by literature evidence, and discuss testing options in resource-limited settings for the diagnostic workup of pediatric sarcomas. Areas of focus include but are not limited to NTRK -rearranged tumors and relevant germline testing in pediatric sarcomas. [ABSTRACT FROM AUTHOR]