94. Initial efforts of the ClinGen Solid Tumor Taskforce in promoting variant curation in solid tumors into CIViC

Aly Abdelkareem

Laveniya Satgunaseelan

Dr Laveniya Satgunaseelan is a pathologist in the Department of Neuropathology at Royal Prince Alfred Hospital, Sydney. Her main role is in the provision of molecular neuropathology services. Laveniya is an active member of the NIH ClinGen Somatic Cancer Working Group, where she is the co-chair of the Solid Tumor Taskforce and Histone H3 Somatic Cancer Variant Curation Expert Panel. She also serves as editor of the CNS chapter of the Compendium of Cancer Genomic Aberrations (CCGA). Locally, Laveniya is the current secretary/treasurer of the Australia and New Zealand Society of Neuropathology.


Laveniya Satgunaseelana, Madina Sukhanovab, Gokce Torunerc, Arpad Danosd, Destiney Allene, Lauren Akessonf, Laura Corsong, Haleh Farzanmehrh, Ariana Gonzalezi, Cameron Grisdalej, Haluk Kavusk, Yuwen Lil, Tracy Livelym, Marilena Melasn, Jason Merkero, Mamta Raop, Shamini Selvarajahq, Zonggao Shir, Dmitriy Sonkinm, Elizabeth Spiteris, Heather Williamst, Xiaonan Zhaou, Yiming Zhongv, Jason Salibad, Obi Griffithd, Malachi Griffithd, Ian Kingq

aRoyal Prince Alfred Hospital, Sydney, Australia; bFeinberg School of Medicine, Northwestern University, Chicago, IL, United States; MD  Anderson Cancer Center, Houston, TX, United States; dWashington University School of Medicine, St. Louis, MO, United States; eQuest Diagnostics, San Juan Capistrano, CA, United States; fMelbourne Pathology, RMH, Melbourne, VIC, Australia; gPrecision Oncology Consultant, Boston, MA, United States; hGeneX Laboratory Professional Corp, Irvine, CA, United States; iHeritas, Santa Fe, Argentina; jCanada’s Michael Smith Genome Sciences Centre, Vancouver, BC, Canada; kGeisinger Medical Center, Danville, PA, United States; lTulane University School of Medicine, New Orleans, LA, United States; mNational Cancer Institute, Rockville, MD, United States; nNew York Genome Center, New York, NY, United State; oUniversity of North Carolina School of Medicine, Chapel Hill, NC, United States; pMemorial Sloan Kettering, New York, NY, United States; qPrincess Margaret Cancer Centre, Toronto, ONT, Canada; rSt. Jude Children’s Research Hospital, Memphis, TN, United States; sStanford Medicine, Palo Alto, CA, United States; tCache DNA, Inc., San Carlos, CA, United States; uBaylor College of Medicine, Baylor Genetics, Houston, TX, United States; vThe Children’s Hospital of Philadelphia, Philadelphia, PA, United States

The Clinical Genome Resource (ClinGen) Somatic Clinical Domain Working Group (CDWG) (https://www.clinicalgenome.org/working-groups/clinical-domain/somatic-cancer-cdwg/) is an international multi-institutional effort to develop and standardize data curation guidelines for somatic genomic alterations in cancer. The recognition of a demanded but missing focus specific for solid tumors, in light of expanded testing options and the increased complexity of tumor classification systems that incorporate molecular information, led to the formation of the Somatic Cancer Solid Tumor Taskforce (STT) under the CDWG. The newly formed STT comprises 55 members from academia and industry, combining their expertise in variant curation in solid tumors. Our primary aim is the curation of somatic genetic alterations in solid tumors into the Clinical Interpretation of Variants in Cancer database (CIViC; civicdb.org), with the objective of supporting the clinical interpretation of difficult to curate alterations. A curation focus (e.g., EGFR fusions) is chosen at each quarter with monthly reviews of CIViC evidence items contributed by STT members. Half yearly, assertions of clinical significance regarding the alterations are formulated in CIViC. Where curation challenges persist, formation of a Somatic Cancer Variant Curation Expert Panel (SC-VCEP) will be recommended. For example, an SC-VCEP focusing on curation of single nucleotide variants in the FGFR3 gene in urothelial cancer is currently active in Step 2 of the ClinGen SC-VCEP approval process, developing classification rules specific to somatic variants in FGFR3. The STT is seeking invaluable input from the CGC community on solid tumor areas presenting clinical interpretation challenges.