Clinicopathologic Features of Non–Small-Cell Lung Cancer Harboring an NTRK Gene Fusion
Autor: | Eric B. Haura, A. John Iafrate, Alexander Drilon, Alexander I. Spira, Shivaani Kummar, Sai-Hong Ignatius Ou, Martin S. Taylor, Long P. Le, Viola W. Zhu, Jochen K. Lennerz, Mari Mino-Kenudson, Ryma Benayed, Maria E. Arcila, Theresa A. Boyle, Robert C. Doebele, Anna F. Farago, Alice T. Shaw, Nora Horick, Dara L. Aisner |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cancer Research business.industry Kinase Tropomyosin receptor kinase A medicine.disease Fusion gene 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Text mining Oncology 030220 oncology & carcinogenesis Trk receptor Cancer research medicine Non small cell business Lung cancer Gene |
Zdroj: | JCO Precision Oncology. :1-12 |
ISSN: | 2473-4284 |
Popis: | 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. |
Databáze: | OpenAIRE |
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