Whole exome sequencing identifies driver mutations in asymptomatic computed tomography-detected lung cancers with normal karyotype

Research output: Contribution to journalArticle


The efficacy of curative surgery for lung cancer could be largely improved by non-invasive screening programs, which can detect the disease at early stages. We previously showed that 18% of screening-identified lung cancers demonstrate a normal karyotype and, following high-density genome scanning, can be subdivided into samples with 1) numerous; 2) none; and 3) few copy number alterations. Whole exome sequencing was applied to the two normal karyotype, screening-detected lung cancers, constituting group 2, as well as normal controls. We identified mutations in both tumors, including KEAP1 (commonly mutated in lung cancers) in one, and TP53, PMS1, and MSH3 (well-characterized DNA-repair genes) in the other. The two normal karyotype screening-detected lung tumors displayed a typical lung cancer mutational profile that only next generation sequencing could reveal, which offered an additional contribution to the over-diagnosis bias concept hypothesized within lung cancer screening programs.

Original languageEnglish
Pages (from-to)152-155
Number of pages4
JournalCancer genetics
Issue number4
Publication statusPublished - Apr 1 2015



  • CT-screening
  • Mutation instability in lung cancer
  • Normal karyotype
  • Over-diagnosis
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology
  • Medicine(all)

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