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Open AccessArticle

Molecular Subtyping and Prognostic Assessment Based on Tumor Mutation Burden in Patients with Lung Adenocarcinomas

by 1,2,3,†, 2,3,†, 2,3, 2,3, 2,3, 2,3, 2, 1,2,3, 2,3, 2,3 and Xiuqing Zhang 1,2,3,*
1
School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China
2
BGI-Shenzhen, Shenzhen 518083, China
3
China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(17), 4251; https://doi.org/10.3390/ijms20174251
Received: 4 July 2019 / Revised: 18 August 2019 / Accepted: 26 August 2019 / Published: 30 August 2019
(This article belongs to the Section Molecular Oncology)
The distinct molecular subtypes of lung cancer are defined by monogenic biomarkers, such as EGFR, KRAS, and ALK rearrangement. Tumor mutation burden (TMB) is a potential biomarker for response to immunotherapy, which is one of the measures for genomic instability. The molecular subtyping based on TMB has not been well characterized in lung adenocarcinomas in the Chinese population. Here we performed molecular subtyping based on TMB with the published whole exome sequencing data of 101 lung adenocarcinomas and compared the different features of the classified subtypes, including clinical features, somatic driver genes, and mutational signatures. We found that patients with lower TMB have a longer disease-free survival, and higher TMB is associated with smoking and aging. Analysis of somatic driver genes and mutational signatures demonstrates a significant association between somatic RYR2 mutations and the subtype with higher TMB. Molecular subtyping based on TMB is a potential prognostic marker for lung adenocarcinoma. Signature 4 and the mutation of RYR2 are highlighted in the TMB-High group. The mutation of RYR2 is a significant biomarker associated with high TMB in lung adenocarcinoma. View Full-Text
Keywords: Tumor mutation burden; molecular subtype; lung adenocarcinomas; RYR2 Tumor mutation burden; molecular subtype; lung adenocarcinomas; RYR2
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MDPI and ACS Style

Wang, C.; Liang, H.; Lin, C.; Li, F.; Xie, G.; Qiao, S.; Shi, X.; Deng, J.; Zhao, X.; Wu, K.; Zhang, X. Molecular Subtyping and Prognostic Assessment Based on Tumor Mutation Burden in Patients with Lung Adenocarcinomas. Int. J. Mol. Sci. 2019, 20, 4251.

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