Virtual Library

Start Your Search

Ming Wu



Author of

  • +

    P37 - Pathology - Biomarker Testing (ID 107)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P37.01 - Detection of NTRK Rearrangements by Next-Generation Sequencing in Chinese Lung Carcinoma Patients (ID 1669)

      00:00 - 00:00  |  Presenting Author(s): Ming Wu

      • Abstract
      • Slides

      Introduction

      Neurotrophic receptor kinase (NTRK) fusions involving NTRK1, NTRK2 and NTRK3 are oncogenic drivers in a broad range of adult and pediatric tumor types. Despite of their low frequencies among various tumor populations, NTRK fusions have been recognized as actionable biomarkers to predict response to tropomyosin receptor kinase (TRK) inhibitors, making their routine detection an evolving clinical priority. In this study, next-generation sequencing (NGS) was applied to explore NTRK fusions in Chinese lung carcinoma patients, and to explore the relationships between NTRK fusions and clinicopathological features.

      Methods

      Formalin-fixed, paraffin-embedded (FFPE) tumor samples were collected from 6290 Chinese lung cancer patients and subjected to a clinical-grade NGS-based 450 gene panel testing carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Gene fusions were measured by a novel NGS algorithm named as OriFusion. Five specimens were carried out pan-TRK IHC assay.

      Results

      In total, 12 specimens (0.19%) were detected with NTRK1 (0.11%), NTRK2 (0.02%) or NTRK3 (0.06%) fusions. The frequencies of NTRK fusions in small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) were detected as 0.43% (1/230) and 0.18% (11/6060), respectively. Among eleven cases of NSCLC, all were adenocarcinoma (0.22%, 11/4909). The NTRK fusion prevalences of patients at stage I, II, III and IV were 0.10%, 0.19%, 0.31% and 0.29%, respectively. NTRK fusions were tended to harbor more frequently in patients with liver (0.75% vs 0.17%, p=0.0889) or intrapulmonary (0.50% vs 0.13%, p=0.0307) metastases. Patients with NTRK fusions were observed significantly younger than those without NTRK fusions (median age: 54 vs. 60, p=0.0785). In the meanwhile, gender, smoking history, tumor mutation burden (TMB), MSI/MMR and PD-L1 expression status were not found to be correlated with NTRK fusion incidences. Five patients were identified with 5 noncanonical fusion partners. Four out of 12 patients with NTRK fusions were verified using IHC assay. However, one known ETV6-NTRK3 fusion was failed to confirm by IHC, which highlighted the necessity of NGS in assisting NTRK fusion detection because of its higher sensitivity and capability. A 63-year old Chinese male with PRDX1 exon5-NTRK1 exon12 fusion was diagnosed as advanced lung adenocarcinoma. After six-month treatment of TRK inhibitor, computed tomography (CT) scanning showed sustained partial response with reduction of lung lesions and disappearance of pleural effusion.

      Conclusion

      Although NTRK fusions occur in lung carcinoma patients across ages, metastases, genders, smoking histories and histologies, its frequencies were significantly higher in younger patients and patients with liver or intrapulmonary metastases. Notably, NGS can detect both canonical and noncanonical NTRK fusions and may suggest more potential candidates who could benefit from TRK inhibitors.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.