Jason Saliba
Abstract
aJason Saliba, Laura B. Corsonb, Jake Leverc, Shivani Golemd, Laveniya Satgunaseelane, David M. Meredithf, Cameron J. Grisdaleg, Kilannin Krysiaka, Mark G. Evansh, Minjie Luoi, Madina Sukhanovaj, Mariam T. Mathewk, Morteza Seifil, Heather E. Williamsm, Kai Lee Yapn, Lauren Akessono, Rashmi Kanagal-Shamannap, Jianling Jiq, Yasmina Jaufeerally Fakimr, Arpad Danosa, Yassmine Akkaris, D. Williams Parsonst, Lynn Schrimlu, Alex H. Wagnerk, Obi L. Griffitha, Malachi Griffitha, Angshumoy Royt, Gordana Racaq, on behalf of the ClinGen Pediatric CancerTaskforce
aWashington University School of Medicine, St. Louis, MO, United States; bPrecision Oncology Consultant, Boston, MA, United States; cUniversity of Glasgow, Glasgow, Scotland; dUniversity of Kansas Medical Center, Kansas City, KS, United States; eRoyal Prince Alfred Hospital and The University of Sydney, Sydney, NSW, Australia; fDana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States; gCanada’s Michael Smith Genome Sciences Centre, Vancouver, BC, Canada; hCaris Life Sciences, Phoenix, AZ, United States; iChildren’s Hospital of Philadelphia and University of Penn, Philadelphia, PA, United States; jFeinberg School of Medicine and Northwestern University, Chicago, IL, United States; kNationwide Children’s Hospital and Ohio State University, Columbus, OH, United States; lWisconsin State Laboratory of Hygiene, University of Wisc., Madison, WI, United States; mCache DNA Inc., San Carlos, CA, United States; nAnn & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, United States; oUniversity of Melbourne, Melbourne, VI, Australia; pThe University of Texas MD Anderson Cancer Center, Houston, TX, United States; qChildren’s Hospital Los Angeles, Los Angeles, CA, United States; rUniversity of Mauritius, Reduit, Moka, Mauritius; sNationwide Children’s Hospital and Ohio State University, Columbus, OH, United States; tBaylor College of Medicine, Houston, TX, United States; uUniversity of Maryland School of Medicine, Baltimore, MD, United States; ClinGen Somatic CDWG, St. Louis, MO, United States
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.