Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway. Academic Article uri icon

Overview

abstract

  • RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.

authors

publication date

  • February 2, 2021

Research

keywords

  • Adenocarcinoma of Lung
  • Kelch-Like ECH-Associated Protein 1
  • Lung Neoplasms
  • Tachykinins
  • Whole Genome Sequencing

Identity

PubMed Central ID

  • PMC8009291

Scopus Document Identifier

  • 85100408037

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.108707

PubMed ID

  • 33535033

Additional Document Info

volume

  • 34

issue

  • 5