Synchronous driver gene alterations (EGFR L858R, T790M, and ROS1) rearrangements in a patient with early-stage lung adenocarcinoma


      Concurrent EGFR mutation and ROS1 rearrangement is a rare event in early-stage non-small-cell lung cancer. In addition, a co-occurring de novo EGFR T790M mutation in such a case is extremely rare. We encountered a 72-year-old woman who developed 3 early-stage lung lesions synchronously, one each harboring EGFR L858R, ROS1 rearrangement, and EGFR L858R and de novo T790M. These three nodules were pathologically time-matched lepidic predominant adenocarcinoma with small invasive lesions, which may reflect the concept of field cancerization with driver mutations.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Choi Y.L.
        • Takeuchi K.
        • Soda M.
        • et al.
        Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer.
        Cancer Res. 2008; 68: 4971-4976
        • Fukui T.
        • Yatabe Y.
        • Kobayashi Y.
        • et al.
        Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene.
        Lung Cancer. 2012; 77: 319-325
        • Wang M.
        • Herbst R.S.
        • Boshoff C.
        Toward personalized treatment approaches for non-small-cell lung cancer.
        Nat Med. 2021; 27: 1345-1356
        • Skoulidis F.
        • Heymach J.V.
        Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy.
        Nat Rev Cancer. 2019; 19: 495-509
        • Sun S.
        • Du W.
        • Sun Q.
        • et al.
        Driver gene alterations profiling of Chinese non-small cell lung cancer and the effects of co-occurring alterations on immunotherapy.
        Cancer Med. 2021;
        • Zhao Y.
        • Wang S.
        • Yang Z.
        • et al.
        Co-occurring potentially actionable oncogenic drivers in non-small cell lung cancer.
        Front Oncol. 2021; 11665484
        • Cardarella S.
        • Ortiz T.M.
        • Joshi V.A.
        • et al.
        The introduction of systematic genomic testing for patients with non-small-cell lung cancer.
        J Thorac Oncol. 2012; 7: 1767-1774
        • Deng H.
        • Liu C.
        • Zhang G.
        • Wang X.
        • Liu Y.
        Lung adenocarcinoma with concurrent ALK and ROS1 rearrangement: a case report and review of the literatures.
        Pathol Res Pract. 2018; 214: 2103-2105
        • Ju L.
        • Han M.
        • Zhao C.
        • EGFR Li X.
        KRAS and ROS1 variants coexist in a lung adenocarcinoma patient.
        Lung Cancer. 2016; 95: 94-97
        • Zhang X.
        • Feng J.
        • Su X.
        • Lei Y.
        • Wu W.
        • Cheng X.
        Next generation sequencing reveals a synchronous trilateral lung adenocarcinoma case with distinct driver alterations of EGFR 19 deletion or EGFR 20 insertion or EZR-ROS1 fusion.
        Onco Targets Ther. 2020; 13: 12667-12671
        • Zhang Y.
        • Wang H.
        • Wang X.
        • Li S.
        • Fang H.
        Precision treatment of advanced lung adenocarcinoma with coexisting EGFR, ALK, and ROS1 mutations: a case report.
        Clin Lung Cancer. 2021; 22: e699-e702
        • Zhu Y.C.
        • Xu C.W.
        • Ye X.Q.
        • et al.
        Lung cancer with concurrent EGFR mutation and ROS1 rearrangement: a case report and review of the literature.
        Onco Target Ther. 2016; 9: 4301-4305
        • Tang Z.
        • Zhang J.
        • Lu X.
        • et al.
        Coexistent genetic alterations involving ALK, RET, ROS1 or MET in 15 cases of lung adenocarcinoma.
        Mod Pathol. 2018; 31: 307-312
        • Basu A.K
        DNA damage, mutagenesis and cancer.
        Int J Mol Sci. 2018; 19
        • Cheng Y.I.
        • Gan Y.C.
        • Liu D.
        • Davies M.P.A.
        • Li W.M.
        • Field J.K.
        Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review.
        BMC Cancer. 2019; 19: 1068
        • Giustini N.
        • Bazhenova L.
        Recognizing prognostic and predictive biomarkers in the treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs).
        Lung Cancer (Auckland, NZ). 2021; 12: 21-34
        • Nassiri M.
        • Kooshyar M.M.
        • Roudbar Z.
        • Mahdavi M.
        • Doosti M.
        Genes and SNPs associated with non-hereditary and hereditary colorectal cancer.
        Asian Pac J Cancer Prev. 2013; 14: 5609-5614
        • Hasty P.
        • Montagna C.
        Chromosomal rearrangements in cancer: detection and potential causal mechanisms.
        Mol Cell Oncol. 2014; 1
        • Zhang T.
        • Joubert P.
        • Ansari-Pour N.
        • et al.
        Genomic and evolutionary classification of lung cancer in never smokers.
        Nat Genet. 2021; 53: 1348-1359
        • Hecht S.S.
        Tobacco carcinogens, their biomarkers and tobacco-induced cancer.
        Nat Rev Cancer. 2003; 3: 733-744