Identification of somatic alterations in stage I lung adenocarcinomas by next‐generation sequencing

Abstract

Adenocarcinoma is the most common type of lung cancer. Somatic mutations in the early stage of this disease have a tight relationship with tumor initiation and potentially activate downstream pathways that are implicated in tumor progression. In this study, we performed whole genome and exome sequencing of tumor and adjacent normal tissue from 10 patients with stage I lung adenocarcinoma. EGFR (4/10 tumors), BCHE (3/10), and TP53 (2/10) were identified recurrently with validated tumor-specific non-synonymous mutations; and the remaining mutations were specific to individual tumors. Computational methods were used to evaluate the potential effect of non-synonymous mutations on protein function, and putative driver mutation in genes such as SDK1 was predicted. Cell adhesion was the most enriched biological process in gene set analysis using the DAVID database. Copy number amplification at 12q15, which includes MDM2, was identified as a recurrent somatic alteration in 4 of 10 tumors. These findings provided additional information for understanding early-stage lung adenocarcinomas.

Genomic alterations of ground-glass nodular lung adenocarcinoma

“…In agreement with previous studies of early lung adenocarcinoma, EGFR mutations are major driver mutations in this study 12 , 13 . However, the frequency of EGFR mutation in this study (89%) was higher than those of previous studies (30–40% in Asian patients with early lung adenocarcinoma) 12 , 13 , for several possible reasons.…”

“…In agreement with previous studies of early lung adenocarcinoma, EGFR mutations are major driver mutations in this study 12 , 13 . However, the frequency of EGFR mutation in this study (89%) was higher than those of previous studies (30–40% in Asian patients with early lung adenocarcinoma) 12 , 13 , for several possible reasons. First, previous studies have shown that ground-glass nodular lung adenocarcinoma has more frequent EGFR mutations (up to about 63%) compared to other types of adenocarcinoma 13 , 14 .…”

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

“…3 ). Similar analysis was also applied to 10 previously reported stage I Chinese lung adenocarcinomas with WGS data 22 . Three high confident signatures from these tumours were identified, which show high correlation with signature 1, signature 3 and signature 4 that were extracted from 24 Chinese lung adenocarcinomas at late stage and 22 European lung adenocarcinomas.…”

Next-Generation Technologies for Multiomics Approaches Including Interactome Sequencing

“…In genomic analysis, somatic mutations are detected using whole-genome sequencing or whole-exome sequencing. In whole-genome sequencing, somatic mutations (e.g., single nucleotide polymorphisms or insertion-deletion mutations) are identified by sequencing the entire genome, and this approach has been used to identify several somatic mutations in various cancers [ 4 , 5 ].…”