TY - JOUR
T1 - Molecular subtyping and prognostic assessment based on tumor mutation burden in patients with lung adenocarcinomas
AU - Wang, Changzheng
AU - Liang, Han
AU - Lin, Cong
AU - Li, Fuqiang
AU - Xie, Guoyun
AU - Qiao, Sitan
AU - Shi, Xulian
AU - Deng, Jianlian
AU - Zhao, Xin
AU - Wu, Kui
AU - Zhang, Xiuqing
N1 - Funding Information:
Funding: This research was funded by the National Key Research and Development Program of China (No. 2016YFC0902301) and the Science, Technology, and Innovation Commission of Shenzhen Municipality under grant No. JCYJ20170817145454378 and No. JCYJ20160531193931852.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - Lung adenocarcinomas
KW - Molecular subtype
KW - RYR2
KW - Tumor mutation burden
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U2 - 10.3390/ijms20174251
DO - 10.3390/ijms20174251
M3 - Article
C2 - 31480292
AN - SCOPUS:85071744346
SN - 1661-6596
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 17
M1 - 4251
ER -