Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway

TCGA Research Network

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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.

Original languageEnglish (US)
Article number108707
JournalCell Reports
Volume34
Issue number5
DOIs
StatePublished - Feb 2 2021

Keywords

  • TCGA
  • driver
  • genome analysis
  • lung adenocarcinoma
  • noncoding
  • oncogene
  • precision oncology
  • structural variation
  • tumor suppressor
  • whole genome sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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