Journal Article

IDH‐mutated astrocytomas with 19q‐loss constitute a subgroup that confers better prognosis

Higuchi, Fumi, Otani, Ryohei, Matsuda, Hadzki, Mukasa, Akitake, Ueki, Keisuke, Ichimura, Koichi, Kim, Phyo, Nomura, Masashi, Uzuka, Takeo, Tanaka, Shota

2018

Overview

IDH‐mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II‐IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next‐generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH‐mutated gliomas, 12 were 1p‐intact/19q‐intact (anaplastic astrocytomas [AA]), 7 were 1p‐intact/19q‐loss (AA), and 23 showed 1p/19q‐codeletion (anaplastic oligodendrogliomas). Of the 88 IDH‐wild type glioblastomas (GBMs), 14 showed 1p‐intact/19q‐loss status. All of the seven 1p‐intact/19q‐loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q‐loss AAs had regions presenting oligodendroglioma‐like morphology, and were associated with significantly longer overall survival compared to 19q‐intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q‐loss GBM and 19q‐intact GBM (P = .4). In a case of 19q‐loss AA, both oligodendroglial morphology and 19q‐loss disappeared after recurrence, possibly indicating correlation between 19q‐loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH‐mutated astrocytomas harboring 19q‐loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q‐intact astrocytomas. Even after the introduction of the WHO 2016 classification, heterogeneity within each category still exists, and the next challenges would include whether we can further refine subtyping of gliomas. Our analysis of 170 diffuse gliomas suggested that there appeared to be a subgroup of IDH‐mutated astrocytomas characterized by isolated 19q‐loss, oligodendroglial morphology and significantly better prognosis compared to other 19q‐intact astrocytomas, providing with a new genetic‐morphological‐clinical association that may characterize a small but distinct subtype within anaplastic astrocytoma.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: 19q / Adult / Aged / Astrocytoma / Astrocytoma - genetics / Astrocytoma - mortality / Astrocytoma - pathology / Brain cancer / Brain Neoplasms - genetics / Brain Neoplasms - mortality / Brain Neoplasms - pathology / Brain tumors / Cancer therapies / Chromosome Deletion / Chromosomes, Human, Pair 1 - genetics / Chromosomes, Human, Pair 19 - genetics / Classification / Cloning / Deoxyribonucleic acid / DNA / Female / Genetic analysis / Genomes / Glioma / Humans / Isocitrate Dehydrogenase - genetics / Kaplan-Meier Estimate / Male / Medical prognosis / Medical research / Middle Aged / Morphology / Mutation / neuropil‐like island / Oligodendroglioma / Original / p53 Protein / Physical characteristics / Prognosis / R&D / Radiation therapy / Research & development / Survival / Tumors / WHO 2016