NTRK and ALK rearrangements in malignant pleural mesothelioma, pulmonary neuroendocrine tumours and non-small cell lung cancer.

Autor: Leal JL; Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Peters G; ANU Medical School, Australian National University, Australian Capital Territory, Australia; Department of Medical Oncology, The Canberra Hospital, Australian Capital Territory, Australia., Szaumkessel M; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia., Leong T; Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia; Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia., Asadi K; Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia., Rivalland G; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia., Do H; Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia., Senko C; Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia., Mitchell PL; Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia., Quing CZ; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia., Dobrovic A; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; University of Melbourne Department of Surgery, Austin Health, Heidelberg, Victoria, Australia., Thapa B; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia; Department of Cardiothoracic Vascular Surgery, Manmohan Cardiothoracic Vascular and Transplant Centre, Kathmandu, Nepal., John T; Department of Medical Oncology, Austin Health, Olivia Newton-John Cancer and Wellness Centre, Heidelberg, Victoria, Australia; Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia. Electronic address: tom.john@petermac.org.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2020 Aug; Vol. 146, pp. 154-159. Date of Electronic Publication: 2020 May 24.
DOI: 10.1016/j.lungcan.2020.05.019
Abstrakt: Objectives: Gene rearrangements involving NTRK1, NTRK2, NTRK3, ROS1 and ALK have been identified in many types of cancer, including non-small cell lung cancer (NSCLC). Data in malignant pleural mesothelioma (MPM), lung neuroendocrine tumors (NETs) and small-cell lung cancer (SCLC) are lacking. Given the activity of NTRK, ROS-1 and ALK inhibitors in tumors harboring gene fusions, we sought to explore such rearrangements in these less common tumors in addition to NSCLC.
Methods: Archival tumor tissue from patients with MPM, lung NETs, SCLC and NSCLC were used to create tissue microarrays. Immunohistochemistry (IHC) was performed using a cocktail of antibodies against TRK, ROS1 and ALK. IHC positive samples underwent RNA sequencing using the ArcherDX FusionPlex CTL diagnostic assay. Clinical data were obtained through retrospective chart review.
Results: We performed IHC on 1116 samples: 335 MPMs, 522 NSCLCs, 105 SCLCs and 154 lung NETs. There were 23 IHC positive cases (2.1%) including eight MPMs (2.4%), eight NETs (5.2%), five SCLC (4.8%) and two NSCLC (0.4%). The following fusions were detected: one MPM with an NTRK ex10-TPM3 ex8, another MPM with an ALK ex20-EML4ex13, one lung intermediate-grade NET (atypical carcinoid) with an ALK ex20-EML4 ex6/intron6, and two NSCLCs with an ALK ex20-EML4 ex6/intron6 rearrangement. None of the patients received targeted treatment.
Conclusions: To our knowledge, we report for the first time NTRK and ALK rearrangements in a small subset of MPM. An ALK rearrangement was also detected in lung intermediate-grade NET (or atypical carcinoid). Our data suggest that IHC could be a useful screening test in such patients to ensure that all therapeutic strategies including targeted therapy are utilized.
Competing Interests: Declaration of Competing Interest Dr. Leal has received investigation grants from MSD, Roche, Boheringer Ingelheim, Pfizer, Astra Zeneca and BMS; and has received personal fees from MSD, Roche, Boheringer Ingelheim, Pfizer, Astra Zeneca, BMS, Sanofi, Elly-Lilly and Tecnofarma. All this is outside of the submitted work. Dr. Leong has received personal fees from Pfizer and Astra Zeneca; has received non-financial support from Biocardis Idylla and Roche, all outside of the submitted work. Dr. Rivalland has received personal fees from Astra Zeneca and MSD, and non-financial support from Pfizer, all outside of the submitted work. Dr. Mitchell has received grants from Astra Zeneca and BMS; has received personal fees from Astra Zeneca, BMS, Amgen, Roche, MSD, Merck, Boheringer Ingelheim and Pfizer; and non-financial support from Astra Zeneca, BMS and Roche. Dr. John has received personal fees from Ignyta, Roche, Astra Zeneca, Novartis, Pfizer, BMS and Merck, all outside of the submitted work.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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