Distinct molecular profile and outcome of oligodendroglioma, IDH-mutant, 1p/19q-codeleted and TERTp-wildtype: a grade 1 oligodendroglioma of young patients?
Filippo Nozzoli, Ramin Rahmanzade, Simone Schmid, Leonille Schweizer, Daniel Schrimpf, Dennis Friedel, Kirsten Göbel, David E Reuss, Rouzbeh Banan, Philipp Sievers, Stefan Pusch, Henri Bogumil, Felix Hinz, Abigail K Suwala, Fuat Kaan Aras, Lukas Friedrich, Simona Osella-Abate, Alessia Andrea Ricci, Alessandra Macciotta, Thorsten Simon, Gudrun Fleischhack, Kathy Keyvani, Jordan R Hansford, Dong-Anh Khuong-Quang, Philippe Schucht, Theoni Maragkou, Tareq A Juratli, Matthias Meinhardt, Sabrina Zechel, Christine Stadelmann, Roland Coras, Oliver W Sakowitz, Benjamin Goeppert, Jens Schittenhelm, Nima Etminan, Miriam Ratliff, Christel Herold-Mende, Stefan M Pfister, Wolfgang Wick, Sandro M Krieg, Andreas von Deimling, Felix Sahm, Luca Bertero
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引用次数: 0
Abstract
Background: Oligodendrogliomas, characterized by isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletion, often exhibit telomerase reverse transcriptase promoter (TERTp) mutations which have been linked to telomere maintenance (TM) and tumour proliferation. Although there are a few reports on a TERTp-wildtype subset of these tumours in adolescents and young adults, the frequency, molecular characteristics and prognostic implications of TERTp-wildtype status in oligodendrogliomas remains elusive.
Methods: We retrospectively analysed 166 IDH-mutant and 1p/19q-codeleted oligodendroglioma cases through comprehensive histopathological review and molecular analyses, including Sanger sequencing, DNA methylation profiling and whole exome sequencing (WES).
Results: A TERTp-wildtype status was observed in 20/166 cases (12.0%) and was significantly associated with noticeably young age (p<0.001), CNS WHO grade 2 (p=0.003), and the absence of additional DNA copy number variations (CNVs) beyond the pathognomonic 1p/19q codeletion (p<0.001). Epigenetic profiling demonstrated TERTp-wildtype tumours shaped a distinct subgroup at the utmost periphery of TERTp-mutant oligodendrogliomas. Methylation analysis of the upstream and proximal TERTp regions revealed that, in line with the absence of genetic alterations, epigenetic regulation does not favour TERT overexpression in TERTp-wildtype oligodendrogliomas. WES showed no TM-related genes alterations in TERTp-wildtype cases. Cox regression analysis confirmed TERTp-wildtype status as an independent prognostic factor for more favourable progression-free survival (PFS) (p=0.009).
Conclusions: In conclusion, "oligodendroglioma, IDH-mutant, 1p/19q-codeleted and TERTp-wildtype" represents a distinct molecular subgroup associated with younger age and a better clinical course compared to CNS WHO grade 2 oligodendrogliomas.
背景：少突胶质细胞瘤以异柠檬酸脱氢酶（IDH）突变和1p/19q编码为特征，常表现出端粒酶逆转录酶启动子（TERTp）突变，该突变与端粒维持（TM）和肿瘤增殖有关。虽然有一些关于这些肿瘤在青少年和年轻人中的tertp野生型亚群的报道，但tertp野生型状态在少突胶质细胞瘤中的频率、分子特征和预后意义仍然难以捉摸。方法：对166例idh突变和1p/19q编码少突胶质细胞瘤患者进行回顾性分析，包括Sanger测序、DNA甲基化分析和全外显子组测序（WES）。结果：在20/166例（12.0%）中观察到tertp -野生型状态，并且与明显的年轻年龄显著相关(p结论：总之，与CNS WHO 2级少突胶质细胞瘤相比，“少突胶质细胞瘤，idh突变，1p/19q编码和tertp -野生型”代表了与年轻年龄和更好的临床病程相关的独特分子亚群。
期刊介绍：
Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field.
The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.
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