Transcriptomic Landscape of Lower Grade Glioma Based on Age-Related Non-Silent Somatic Mutations.

Youngjoon Park,Kyoung Su Sung,Ju Won Ahn,So Jung Hwang,Su Jung Kang,Suwan Kim,Jeong Min Sim,Song-Hee Han,Jaejoon Lim,Jeongman Park

doi:10.3390/curroncol28030210

Youngjoon Park, Kyoung Su Sung + Show 8 more

Open Access

https://doi.org/10.3390/curroncol28030210

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Abstract

Glioma accounts for 80% of all malignant brain tumours and is the most common adult primary brain tumour. Age is an important factor affecting the development of cancer, as somatic mutations accumulate with age. Here, we aimed to analyse the significance of age-dependent non-silent somatic mutations in glioma prognosis. Histological tumour grade depends on age at diagnosis in patients with IDH1, TP53, ATRX, and EGFR mutations. Age of patients with wild-type IDH1 and EGFR increased with increase in tumour grade, while the age of patients with IDH1 or EGFR mutation remained constant. However, the age of patients with EGFR mutation was higher than that of patients with IDH1 mutation. The hierarchical clustering of patients was dominantly separated by IDH1 and EGFR mutations. Furthermore, patients with IDH1 mutation were dominantly separated by TP53 and ATRX double mutation and its double wild-type counterpart. The age of patients with ATRX and TP53 mutation was lower than that of patients with wild-type ATRX and TP53. Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. Unlike IDH1 mutant, IDH1 wild-type showed upregulation of expression of epithelial mesenchymal transition associated genes.

Highlights

Glioma, accounting for 80% of all malignant brain tumours, is the most common primary brain tumour in adults [1], and is usually treated using radiation therapy and using Temozolomide treatment after maximal safe resection [2]
We investigated the effects of age at which non-silent somatic mutations occurred on patient prognosis and analysed their transcriptomic significance and their biological mechanisms or pathways using The Cancer Genome Atlas (TCGA)
Identification of Age-Related Non-Silent Mutations in Lower Grade Glioma (LGG) and Clinical data and non-silent somatic mutation data by multi-centre mutation calling (MC3) from TCGA were used to identify somatic mutations associated with age

Summary

Introduction

Glioma, accounting for 80% of all malignant brain tumours, is the most common primary brain tumour in adults [1], and is usually treated using radiation therapy and using Temozolomide treatment after maximal safe resection [2]. LGG has a better prognosis than GBM, and the efficacy of treatment depends on the molecular subtype of LGG in perspective of overall survival (OS) and progression free survival. GBM has poor prognosis, and the development of new treatment methods based on its molecular characteristics is difficult because of infiltrative and integrative characteristics of normal brain tissues [3,4]. Age is an important factor affecting the development of cancer. Most adult cancers develop exponentially with age [5], owing to the accumulation of somatic mutations [5,6,7]

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