@article{98cc68307b504533a1e02e2a598bb327,
title = "Standardized evidence-based approach for assessment of oncogenic and clinical significance of NTRK fusions",
abstract = "Gene fusions involving the neurotrophic receptor tyrosine kinase genes NTRK1, NTRK2, and NTRK3, are well established oncogenic drivers in a broad range of pediatric and adult tumors. These fusions are also important actionable markers, predicting often dramatic response to FDA approved kinase inhibitors. Accurate interpretation of the clinical significance of NTRK fusions is a high priority for diagnostic laboratories, but remains challenging and time consuming given the rapid pace of new data accumulation, the diversity of fusion partners and tumor types, and heterogeneous and incomplete information in variant databases and knowledgebases. The ClinGen NTRK Fusions Somatic Cancer Variant Curation Expert Panel (SC-VCEP) was formed to systematically address these challenges and create an expert-curated resource to support clinicians, researchers, patients and their families in making accurate interpretations and informed treatment decisions for NTRK fusion-driven tumors. We describe a system for NTRK fusion interpretation (including compilation of key elements and annotations) developed by the NTRK fusions SC-VCEP. We illustrate this stepwise process on examples of LMNA::NTRK1 and KANK1::NTRK2 fusions. Finally, we provide detailed analysis of current representation of NTRK fusions in public fusion databases and the CIViC knowledgebase, performed by the NTRK fusions SC-VCEP to determine existing gaps and prioritize future curation activities.",
keywords = "actionable, biomarker, curation, oncogenicity, pathogenicity, reading-frame",
author = "Jason Saliba and Church, {Alanna J.} and Shruti Rao and Arpad Danos and Furtado, {Larissa V.} and Theodore Laetsch and Liying Zhang and Valentina Nardi and Lin, {Wan Hsin} and Ritter, {Deborah I.} and Subha Madhavan and Li, {Marilyn M.} and Griffith, {Obi L.} and Malachi Griffith and Gordana Raca and Angshumoy Roy",
note = "Funding Information: Jason Saliba, Shruti Rao, Arpad Danos, Gordana Raca, Malachi Griffith, Obi L Griffith and the CIViC project are supported by the National Institutes of Health (NIH) and National Cancer Institute (NCI) under Award Number U24CA237719 to Obi L Griffith (with Malachi Griffith as co-PI), including a funding supplement from the Childhood Cancer Data Initiative (CCDI). Malachi Griffith was also supported by the NIH NHGRI under award number R00HG007940 . Funding for ClinGen with co-funding from the National Cancer Institute Grants are as follows: Baylor/Stanford - U24HG009649 , Broad/Geisinger - U24HG006834, and UNC/Kaiser - U24HG009650. Funding Information: Jason Saliba, Shruti Rao, Arpad Danos, Gordana Raca, Malachi Griffith, Obi L Griffith and the CIViC project are supported by the National Institutes of Health (NIH) and National Cancer Institute (NCI) under Award Number U24CA237719 to Obi L Griffith (with Malachi Griffith as co-PI), including a funding supplement from the Childhood Cancer Data Initiative (CCDI). Malachi Griffith was also supported by the NIH NHGRI under award number R00HG007940. Funding for ClinGen with co-funding from the National Cancer Institute Grants are as follows: Baylor/Stanford - U24HG009649, Broad/Geisinger - U24HG006834, and UNC/Kaiser - U24HG009650.AC reports consulting and a member of the medical advisory board for Bayer. TL reports consulting for Bayer, Cellectis, Novartis, Deciphera, Jumo Health, and Y-mAbs Therapeutics and research support from Bayer, Pfizer, and Novartis. LZ reports that family members hold leadership positions and ownership interests of Decipher Medicine. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = jun,
doi = "10.1016/j.cancergen.2022.03.001",
language = "English",
volume = "264-265",
pages = "50--59",
journal = "Cancer Genetics",
issn = "2210-7762",
}