IDH-mutant astrocytoma with an evolutional progression to CDKN2A/B homozygous deletion and NTRK fusion during recurrence: A case report.

Abstract

We reported a case of molecularly defined isocitrate dehydrogenase (IDH)-mutant astrocytoma that recurred twice with aggressive behavior and increased anaplastic morphology. Primary and recurrent tumors were analyzed using custom-made DNA-based cancer gene and RNA-based fusion panels for next-generation sequencing (NGS). NGS analyses revealed that recurrent astrocytoma, in addition to IDH1 and tumor protein 53 mutations detected in the primary lesion, harbored cyclin-dependent kinase inhibitor (CDKN) 2 A/B homozygous deletion and neurotrophic tropomyosin receptor kinase 2 (NTRK2) fusion genes that consisted of golgin A1- and cyclin-dependent kinase 5 regulatory subunit associated protein 2-NTRK2 fusions. Anaplasia and necrosis were observed in the recurrent tumors, but not in the primary lesion. Therefore, the integrative diagnosis was primary IDH-mutant astrocytoma grade 2 and recurrent IDH-mutant astrocytoma grade 4 with NTRK2 fusions. This is a worthwhile report describing a case of IDH-mutant astrocytoma that showed genomic evolution during tumor recurrence. Our report suggests that NTRK fusion and CDKN2A/B homozygous deletion promote high-grade transformation and indicate an unfavorable prognosis of IDH-mutant astrocytoma.

• Authors: Mari Kirishima, Toshiaki Akahane, Nayuta Higa, Shinsuke Suzuki, Shinichi Ueno, Hajime Yonezawa, Hiroyuki Uchida, Ryosuke Hanaya, Koji Yoshimoto, Shohei Shimajiri, Ikumi Kitazono, Akihide Tanimoto
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 239 Pg. 154163 (Nov 2022) ISSN: 1618-0631 [Electronic] Germany
• PMID: 36265224 (Publication Type: Case Reports)
• Copyright: Copyright © 2022. Published by Elsevier GmbH.

Chemical References

• Isocitrate Dehydrogenase
• CDKN2A protein, human
• Cyclin-Dependent Kinase Inhibitor p16

Topics

• Humans
• Isocitrate Dehydrogenase (genetics)
• Homozygote
• Brain Neoplasms (pathology)
• Sequence Deletion
• Astrocytoma (pathology)
• Mutation
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)