Gain of TP53 Mutation in Imatinib-treated SDH-Deficient Gastrointestinal Stromal Tumor and Clinical Utilization of Targeted Next-generation Sequencing Panel for Therapeutic Decision Support. Issue 8 (September 2018)

• Record Type: Journal Article
• Authors: Wei, Christina H.; Pettersson, Jonas; Campan, Mihaela; Chopra, Shefali; Naritoku, Wesley; Martin, Sue E.; Ward, Pamela M.
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 26:Issue 8(2018)
• Publication Date: 2018-09
• Subjects: gastrointestinal stromal tumor -- succinate dehydrogenase deficiency -- next-generation sequencing; Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PAI.0000000000000482
• Languages: English
• ISSNs: 1541-2016

Abstract

Abstract : Patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) have few therapeutic options. Despite lack of KIT or platelet-derived growth factor receptor A ( PDGFRA ) driver mutations, SDH-deficient GISTs display strong expression of KIT by immunohistochemistry and these patients are often treated with tyrosine kinase inhibitors, including imatinib as a first-line therapy. Using a targeted next-generation sequencing panel of mutation hotspots of 50-clinically relevant genes, we investigated (1) concurrence of somatic/actionable mutations and (2) tumor molecular evolution by comparing 2 resection specimens 1.5 years apart while the patient was on imatinib adjuvant therapy. We found the tumors did not harbor KIT, PDGFRA, or any other clinically actionable mutations. However, a TP53 mutation (c.422G>A; p.C141Y) was detected in the second recurrent lesion. This represents the first study to monitor the molecular evolution of a SDH-deficient GIST during adjuvant treatment. These findings emphasize the critical need for next-generation sequencing testing before initiating targeted therapy.