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Title: NTRK and ALK rearrangements in malignant pleural mesothelioma, pulmonary neuroendocrine tumours and non-small cell lung cancer.
Austin Authors: Leal, Jose Luis;Peters, Geoffrey;Szaumkessel, Marcin;Leong, Trishe Y-M;Asadi, Khashayar ;Rivalland, Gareth;Do, Hongdo;Senko, Clare ;Mitchell, Paul L R ;Quing, Chai Zi;Dobrovic, Alexander ;Thapa, Bibhusal ;John, Thomas 
Affiliation: Department of Cardiothoracic Vascular Surgery, Manmohan Cardiothoracic Vascular and Transplant Centre, Kathmandu, Nepal
Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Heidelberg, Victoria, Australia
Department of Medical Oncology, Austin Health, Heidelberg, Victoria, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Department of Surgery, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Anatomical Pathology, St Vincent's Hospital, Fitzroy, Victoria, Australia
ANU Medical School, Australian National University, Australian Capital Territory, Australia
Department of Medical Oncology, The Canberra Hospital, Australian Capital Territory, Australia
Issue Date: Aug-2020
Date: 2020-05-24
Publication information: Lung Cancer 2020; 146: 154-159
Abstract: 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. 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. 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. 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.
DOI: 10.1016/j.lungcan.2020.05.019
ORCID: 0000-0003-3399-5342
Journal: Lung Cancer
PubMed URL: 32540558
Type: Journal Article
Subjects: ALK
Lung neuroendocrine tumors
Non-small cell lung cancer.
Appears in Collections:Journal articles

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