52. ClinGen Pediatric Cancer Taskforce Initiatives to Advance Pediatric Clinical Interpretations Through Expert Curation

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. 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.