Clinicopathologic Features of Non–Small-Cell Lung Cancer Harboring an NTRK Gene Fusion
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Published:2018-11
Issue:2
Volume:
Page:1-12
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ISSN:2473-4284
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Container-title:JCO Precision Oncology
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language:en
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Short-container-title:JCO Precision Oncology
Author:
Farago Anna F.1, Taylor Martin S.1, Doebele Robert C.1, Zhu Viola W.1, Kummar Shivaani1, Spira Alexander I.1, Boyle Theresa A.1, Haura Eric B.1, Arcila Maria E.1, Benayed Ryma1, Aisner Dara L.1, Horick Nora K.1, Lennerz Jochen K.1, Le Long P.1, Iafrate A. John1, Ou Sai-Hong I.1, Shaw Alice T.1, Mino-Kenudson Mari1, Drilon Alexander1
Affiliation:
1. Anna F. Farago and Alice T. Shaw, Massachusetts General Hospital Cancer Center; Martin S. Taylor, Nora K. Horick, Jochen K. Lennerz, Long P. Le, A. John Iafrate, and Mari Mino-Kenudson, Massachusetts General Hospital, Boston, MA; Robert C. Doebele and Dara L. Aisner, University of Colorado, Aurora, CO; Viola W. Zhu and Sai-Hong I. Ou, University of California, Irvine, School of Medicine, Orange; Shivaani Kummar, Stanford University, Palo Alto, CA; Alexander I. Spira, Virginia Cancer Specialists, Fairfax,...
Abstract
Purpose Gene rearrangements that involve NTRK1/2/3 can generate fusion oncoproteins that contain the kinase domains of TRKA/B/C, respectively. These fusions are rare in non–small-cell lung cancer (NSCLC), with frequency previously estimated to be < 1%. Inhibition of TRK signaling has led to dramatic responses across tumor types with NTRK fusions. Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion-positive NSCLCs are not well characterized. Methods We compiled a database of patients with NSCLCs that harbor NTRK fusions. We characterized clinical, molecular, and histologic features with central review of histology. Results We identified 11 patients with NSCLCs that harbor NTRK gene fusions verified by next-generation sequencing and with available clinical and pathologic data. Fusions involved NTRK1 (n = 7) and NTRK3 (n = 4), with five and two distinct fusion partners, respectively. Fifty-five percent of cohort patients were male with a median age at diagnosis of 47.6 years (range, 25.3 to 86.0 years) and a median smoking history of 0 pack-years (range, 0 to 58 pack-years). Seventy-three percent of patients had metastatic disease at diagnosis. No concurrent alterations in KRAS, EGFR, ALK, ROS1, or other known oncogenic drivers were identified. Nine patients had adenocarcinoma, including two with invasive mucinous adenocarcinoma and one with adenocarcinoma with neuroendocrine features; one had squamous cell carcinoma; and one had neuroendocrine carcinoma. By collating data on 4,872 consecutively screened, unique patients with NSCLC, we estimate a frequency of NTRK fusions in NSCLC of 0.23% (95% CI, 0.11% to 0.40%). Conclusion NTRK fusions occur in NSCLCs across sexes, ages, smoking histories, and histologies. Given the potent clinical activity of TRK inhibitors, we advocate that all NSCLCs be screened for NTRK fusions by using a multiplexed next-generation sequencing–based fusion assay.
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
147 articles.
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