IDH-mutant gliomas with additional class-defining molecular events

Autor: Ahrendsen, Jared T., Torre, Matthew, Meredith, David M., Hornick, Jason L., Reardon, David A., Wen, Patrick Y., Yeo, Kee K., Malinowski, Seth, Ligon, Keith L., Ramkissoon, Shakti, Alexandrescu, Sanda
Zdroj: Modern Pathology; July 2021, Vol. 34 Issue: 7 p1236-1244, 9p
Abstrakt: The 2016 WHO classifies IDH-mutant gliomas into oligodendroglioma or diffuse astrocytoma based on co-occurring genetic events. Recent literature addresses the concept of stratifying IDH-mutant gliomas based on prognostically significant molecular events. However, the presence of a second class-defining driver alteration in IDH-mutant gliomas has not been systematically described. We searched the sequencing database at our institutions as well as The Cancer Genome Atlas (TCGA) and cBioPortal for IDH-mutant gliomas with other potentially significant alterations. For each case, we reviewed the clinical information, histology and genetic profile. Of 1702 gliomas tested on our targeted exome sequencing panel, we identified 364 IDH-mutated gliomas, four of which had pathogenic FGFRalterations and one with BRAFV600E mutation. Five additional IDH-mutant gliomas with NTRKfusions were identified through collaboration with an outside institution. Also, a search in the glioma database in cBioPortal (5379 total glioma samples, 1515 cases [28.1%] with IDH1/2mutation) revealed eight IDH-mutated gliomas with FGFR, NTRKor BRAFpathogenic alterations. All IDH-mutant gliomas with dual mutations identified were hemispheric and had a mean age at diagnosis of 36.2 years (range 16–55 years old). Co-occurring genetic events involved MYCN, RBand PTEN. Notable outcomes included a patient with an IDH1/FGFR1-mutated anaplastic oligodendroglioma who has survived 20 years after diagnosis. We describe a series of 18 IDH-mutant gliomas with co-occurring genetic events that have been described as independent class-defining drivers in other gliomas. While these tumors are rare and the significance of these alterations needs further exploration, alterations in FGFR, NTRK, and BRAFcould have potential therapeutic implications and affect clinical trial design and results in IDH-mutant studies. Our data highlights that single gene testing for IDH1in diffuse gliomas may be insufficient for detection of targets with potential important prognostic and treatment value.
Databáze: Supplemental Index
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