Balakumar Shailaja, Pai Rekha, Chacko Ari G, Patel Bimal, Nancy Rachel, Balakrishnan Rajesh, Sarkar Sauradeep, Sampath Gowri, Chacko Geeta
Department of General Pathology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
Department of Neurosurgery, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
Neurol India. 2022 May-Jun;70(3):953-959. doi: 10.4103/0028-3886.349649.
Introduction: Gliomas were previously classified histologically, although now the latest WHO classification incorporates several molecular markers to classify these. Detection of TERT promoter mutations is assuming increased importance due to its relevance to prognostication.
: The aim of this study was to determine the frequency of TERT promoter mutations, association of TERT promoter mutations with other molecular alterations and to assess the role of TERT promoter mutations in overall survival and progression-free survival in relation to histological and molecular glioma subtypes.
This study analyzed a cohort of 107 adult patients with diffuse gliomas, WHO grades II and III and glioblastoma, by immunohistochemistry for IDH and ATRX mutations, FISH for 1p/19q co-deletions and PCR sequencing for TERT promoter mutation. Further, five glioma molecular sub-groups were derived using three molecular alteration and included the sub-groups with: i) IDH mutations only, ii) IDH and TERT mutations only, iii) IDH and 1p/19q co-deletion only, iv) Triple negative, and v) Triple positive.
IDH mutations and 1p/19q co-deletions were individually and significantly associated with an improved progression free (P = 0.001 and P = 0.002, respectively) and overall survival (P = 0.000 and P = 0.005, respectively) in the present cohort of gliomas. TERT promoter mutations occurred frequently in anaplastic oligodendrogliomas (94%), oligodendrogliomas (87.5%) and glioblastomas (54%). Sub-division into molecular sub-groups showed that the triple-positive tumors carried the best prognosis, followed by IDH only, triple negative and finally the TERT mutation only tumors (P < 0.000).
: This indicates that sub-classification using these molecular markers separates tumors into prognostically relevant categories.
引言：胶质瘤以前是根据组织学进行分类的，不过现在最新的世界卫生组织（WHO）分类纳入了多种分子标志物来对其进行分类。由于TERT启动子突变与预后相关，其检测的重要性日益增加。
本研究旨在确定TERT启动子突变的频率、TERT启动子突变与其他分子改变的关联，并评估TERT启动子突变在不同组织学和分子类型的胶质瘤亚型的总生存期和无进展生存期方面的作用。
本研究通过免疫组化检测IDH和ATRX突变、荧光原位杂交（FISH）检测1p/19q共缺失以及PCR测序检测TERT启动子突变，分析了107例WHO II级和III级弥漫性胶质瘤及胶质母细胞瘤成年患者队列。此外，利用三种分子改变将胶质瘤分为五个分子亚组，包括：i）仅IDH突变组，ii）仅IDH和TERT突变组，iii）仅IDH和1p/19q共缺失组，iv）三阴性组，v）三阳性组。
在本胶质瘤队列中，IDH突变和1p/19q共缺失分别与无进展生存期（分别为P = 0.001和P = 0.002）和总生存期（分别为P = 0.000和P = 0.005）的改善显著相关。TERT启动子突变在间变性少突胶质细胞瘤（94%）、少突胶质细胞瘤（87.5%）和胶质母细胞瘤（54%）中频繁出现。分子亚组分析显示，三阳性肿瘤预后最佳，其次是仅IDH突变组、三阴性组，最后是仅TERT突变组（P < 0.000）。
这表明使用这些分子标志物进行亚分类可将肿瘤分为具有预后意义的类别。
