Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
NTRK1 fusion identified by capture-based next-generation sequencing in non-small-cell lung cancer.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20664)
Author(s): Ruiying Zhao, Chan Xiang, Nan Dong, Lianying Guo, Shengji Ma, Yuchen Han; Department of Pathology, Shanghai Chest Hospital., Shanghai, China; Department of Pathology, Shanghai Chest hospital, Shanghai, China
Background: The clinicopathological features and genomic rearrangements of neurotrophic tyrosine kinase receptors (NTRKs) fusion in non-small-cell lung cancer (NSCLC) have not been fully identified. To explore NTRK1 fusion in non-small-cell lung cancer (NSCLC) specimens, and to explore the relationships between the NTRK1 fusion and the clinicopathological features and to identify genomic rearrangements by multiple molecular methods. Methods: In total, 3947 NSCLC specimens were tested for NTRK1 fusion using genomic DNA capture-based NGS. Then, these NTRK1 fusion cases were identified by Oncomine Focus Assay and FISH. The clinicopathological features were analyzed. Results: In total, five specimens (0.13%) were detected NTRK1 fusion. All these five specimens were adenocarcinoma (0.15%, 5/3423), while no NTRK1 fusions were found in 496 squamous cell carcinoma (SCC) cases and 28 adenosquamous carcinoma (ASC) cases. The ages of patients carried NTRK fusion were range from 31-year to 64-year-old. These five NTRK1 fusion cases were two females and three males, four non-smokers and one with 30 years smoking history, three surgical specimens and two small biopsies. Among these three surgical specimens, one was minimally invasive adenocarcinoma and two were invasive adenocarcinoma. One canonical fusion (TPM3-NTRK1) was detected, the other four were noncanonical fusion type (C14orf2-NTRK1, RRNAD1-NTRK1, LOC101060524-NTRK1, ARHGEF11-NTRK1). The RRNAD1-NTRK1 case was coexist with L858R mutation of EGFR, and the ARHGEF11-NTRK1 was coexist with G12A mutation of KRAS. All of these five fusions were confirmed by FISH, while only the canonical TPM3-NTRK1 was confirmed by Oncomine Focus Assay. Conclusions: In summary, NTRK1 fusion is rare in lung adenocarcinoma and does not exist in squamous cell carcinoma or adenosquamous carcinoma cases. Age and gender are not significantly correlated with NTRK1 fusion. NTRK1 fusions were more common in non-smokers. Genomic DNA capture-based NGS can detect both canonical and noncanonical NTRK1 genomic rearrangements. Noncanonical NTRK1 genomic rearrangements need confirmed by other methods such as FISH. NTRK1 fusion may coexist with other canonical driver gene mutation.