Farago, Anna F.;
Taylor, Martin S;
Doebele, Robert Charles;
Spira, Alexander I.;
Boyle, Theresa A;
Haura, Eric B.;
Azimi, Roxana S.;
Shaw, Alice Tsang;
Mino-Kenudson, Mari;
Drilon, Alexander E.
Clinicopathologic features of non-small cell lung cancer (NSCLC) harboring an NTRK gene fusion
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Medientyp:
E-Artikel
Titel:
Clinicopathologic features of non-small cell lung cancer (NSCLC) harboring an NTRK gene fusion
Beteiligte:
Farago, Anna F.;
Taylor, Martin S;
Doebele, Robert Charles;
Spira, Alexander I.;
Boyle, Theresa A;
Haura, Eric B.;
Azimi, Roxana S.;
Shaw, Alice Tsang;
Mino-Kenudson, Mari;
Drilon, Alexander E.
Erschienen:
American Society of Clinical Oncology (ASCO), 2017
Erschienen in:
Journal of Clinical Oncology, 35 (2017) 15_suppl, Seite 11580-11580
Beschreibung:
<jats:p> 11580 </jats:p><jats:p> Background: Gene fusions involving NTRK1/2/3 can generate oncoproteins containing the kinase domains of TRKA/B/C, respectively. Inhibition of TRK signaling has led to dramatic responses across tumor types with NTRK fusions. An estimated 0.1 – 1% of NSCLCs harbor NTRK fusions. To date, clinical and radiographic responses to TRK inhibitors have been reported for 2 NTRK fusion-positive NSCLCs (Farago et al., 2015; Hong et al., 2016). Despite the potential benefit of identifying these fusions, the clinicopathologic features of NTRK fusion NSCLCs are not well characterized. Methods: Physicians across multiple institutions contributed deidentified cases to an NTRK fusion NSCLC database. A central pathologist (M.M.) reviewed tumor histology in cases with available tissue. Results: 10 NSCLC cases with NTRK gene fusions were identified. Of these, TRK kinase domain-containing potentially activating fusions were verified by next-generation sequencing (NGS) in 7, forming the study cohort. Fusions involved NTRK1 (6) and NTRK3 (1) with 6 different partners. Four (57%) patients were male. Median age at diagnosis was 47.6 years (range 27.9 – 86.0). The average smoking pack year history was 8.9 (range 0 to 30). Five (71%) presented with metastatic disease. No concurrent alterations in KRAS, EGFR, ALK, ROS1, or other known drivers were identified in the study cohort cases. On pathologic review of 4 cases, all were adenocarcinoma, including 2 invasive mucinous adenocarcinomas and 1 adenocarcinoma with neuroendocrine features. Of the 3 remaining non-study cohort cases, 1 was a non-kinase domain-containing NTRK1 fusion with a concurrent KRAS G12C mutation, 1 was an NTRK2 intragenic deletion disrupting the exon 18 3’ splice site, and 1 was an NTRK1 alteration detected by FISH but not verified by NGS and with a concurrent HER2 L755P mutation. Conclusions: NTRK fusions occur in both men and women across wide ranges in age and smoking history. We therefore suggest that all NSCLC adenocarcinomas without other oncogenic driver alterations be screened for NTRK fusions. Notably, not all NTRK alterations are activating, requiring validation of the specific position of the fusion. </jats:p>