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

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.