Mosaicism for Receptor Tyrosine Kinase Activation in a Glioblastoma Involving Both PDGFRA Amplification and NTRK2 Fusion. (8th June 2021)

• Record Type: Journal Article
• Authors: Shepherd, Daniel J.; Miller, Tyler E.; Forst, Deborah A.; Jones, Pamela; Nardi, Valentina; Martinez-Lage, Maria; Stemmer-Rachamimov, Anat; Gonzalez, Ramon G.; Iafrate, A. John; Ritterhouse, Lauren L.
• Is Part Of: Oncologist. Volume 26:Number 11(2021)
• Page Start: 919
• Page End: 924
• Publication Date: 2021-06-08
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1002/onco.13835
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : : Rearrangements involving the neurotrophic receptor tyrosine kinase (NTRK) gene family have been reported in diverse tumor types, and NTRK-targeted therapies have recently been approved. In this article, we report a case of a 26-year-old man with an NTRK2 -rearranged isocitrate dehydrogenase-wild-type glioblastoma who showed a robust but temporary response to the NTRK inhibitor larotrectinib. Rebiopsy after disease progression showed elimination of the NTRK2 -rearranged tumor cell clones, with secondary emergence of a PDGFRA -amplified subclone. Retrospective examination of the initial biopsy material confirmed rare cells harboring PDGFRA amplification. Although mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma has been previously described, mosaicism involving a fusion gene driver event has not. This case highlights the potential efficacy of NTRK-targeted treatment in glioblastoma and the implications of molecular heterogeneity in the setting of targeted therapy. Key Points : This case highlights the efficacy of the NTRK inhibitor larotrectinib in treating NTRK -rearranged glioblastoma. This is the first case to demonstrate mosaicism in glioblastoma involving both a fusion gene and amplification for receptor tyrosine kinases. Intratumoral heterogeneity in glioblastoma has significant implications for tumor resistance to targeted therapies. Abstract : This article reports a case of a 26-year-old man with an IDH-wild type glioblastoma mosaic for both NTRK2 fusion and receptor tyrosine kinase amplification. He showed a robust but temporary response to the recently-approved NTRK inhibitor larotrectinib with subsequent outgrowth of a PDGFRA -amplified subclone.