TERT promoter mutations in a cohort of adult gliomas –Clinicopathological correlates
Description
Purpose: This study characterizes diffuse gliomas (WHO grade II, III and IV) to determine the frequency of telomerase reverse transcriptase promoter (TERTp) mutations, association of TERTp mutations with other molecular alterations and to assess the role of TERTp mutation in overall survival and progression free survival in relation to histological and molecular glioma subtypes. Methods: This study analyzed a cohort of 107 adult patients with diffuse gliomas, WHO grades II and III and glioblastoma, by immunohistochemistry for isocitrate dehydrogenase (IDH) and alpha-thalassemia/mental retardation, X-linked (ATRX) mutations, fluorescence in situ hybridization (FISH) for 1p/19q co-deletions and polymerase chain reaction (PCR) sequencing for TERTp mutation. Further, five glioma molecular sub-groups were derived using three molecular alterations and included the sub-groups with: i) IDH mutations only, ii) IDH and TERTp mutation only, iii) IDH and 1p/19q co-deletion only, iv) Triple negative and v) Triple positive. Results: 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. TERTp 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 TERTp mutation only tumors (p-value <0.000). Conclusion: This indicates that sub-classification using these molecular markers separates tumors into prognostically relevant categories.