Epigenetic Alterations Are Associated with Tumor Mutation Burden in Non-small Cell Lung Cancer

Overview

Journal J Immunother Cancer

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2019 Jul 28

PMID 31349879

Citations 28

Authors

Liangliang Cai

Hua Bai

Jianchun Duan

Zhijie Wang

Shugeng Gao

Di Wang

Shuhang Wang

Jun Jiang

Jiefei Han

Yanhua Tian

Xue Zhang

Hao Ye

Minghui Li

Bingding Huang

Jie He

Jie Wang

Affiliations

Soon will be listed here.

Abstract

Background: To profile genomic and epigenomic of a naïve Chinese non-small cell lung cancer (NSCLC) cohort and investigate the association between tumor mutation burden (TMB) and DNA methylation (DNAm) to explore potential alternative/complimentary biomarkers for NSCLC immunotherapies.

Methods: A total of 89 tumor tissues with matched normal tissues from Chinese NSCLC patients were collected and subjected to whole exome sequencing (WES). From comparison, each patient was evaluated for the TMB value and divided into high, medium and low TMB based on TMB tertile distribution and then relatively high and low TMB samples were selected and subjected to DNAm profiling.

Results: Patients in the low (n = 30), medium (n = 29), and high (n = 30) TMB tertiles had 1.1-2.5, 2.5-4.1, and 4.2-13.9 mutations/Mb, respectively. A statistical directly association between differential methylation probes (DMPs) and TMB level was observed in our cohort (r = 0.63, P value =0.0003) and this was confirmed by using TCGA NSCLC dataset (r = 0.43, P value =0.006). Relatively high TMB group (n = 16, 7.5-13.9 mutations/Mb) harbors more differential DMPs while less in relatively low TMB group (n = 13, 1.1-2.4 mutations/Mb). Eight hundred fifty-eight differential methylation regions (DMRs) were found in relatively high TMB group. In addition, 437 genes show DNAm aberrance status in high TMB patient group and 99 have been reported as its association with lung cancer.

Conclusion: To our knowledge, this is the first report for direct link between the methylome alterations and TMB in NSCLCs. High TMB NSCLCs had more DNAm aberrance and copy number variations (CNVs). In addition, the TMB distribution of Chinese NSCLCs population is lower than that of TCGA.

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