Les réarrangements moléculaires : cibles thérapeutiques en cancérologie thoracique Fusion transcripts: Therapeutic targets in thoracic oncology

Five to ten percent of lung adenocarcinoma harbor chromosomal rearrangements affecting the ALK, ROS1, NTRK and RET genes. These rearrangements are associated with the production of fusion transcripts that lead to the synthesis of chimeric proteins with constitutive kinase activity. These abnormal proteins induce an oncogenic dependency that may be targeted by tyrosine kinase inhibitors. In this review, we will summarize the clinical and molecular epidemiology of chromosomal rearrangements affecting ALK, ROS1, NTRK and RET genes. We will describe the mechanisms of resistance to tyrosine kinase inhibitors that have been reported. We will present the molecular techniques that can be used to detect these rearrangements and the strategies set-up by the molecular oncology laboratories to diagnose these genetic alterations. READ ARTICLE

Bulletin du Cancer DOI:10.1016/j.bulcan.2020.05.008

Authors: Audrey Mansuet-Lupo, Simon Garinet, Diane Damotte, Marco Alifano, Hélène Blons, Marie Wislez, Karen Leroy

Review PaperKirk SmithSeptember 1, 2020Rearrangement, Fusion, ALK, ROS1, RET, NTRK

Computed Tomography Imaging Features and Distribution of Metastases in ROS1-rearranged Non–Small-cell Lung Cancer

Background: ROS proto-oncogene 1 (ROS1) rearrangements are a known molecular target in non–small-cell lung cancer (NSCLC). Our goal was to determine whether ROS1-rearranged NSCLC has imaging features and patterns of metastasis, which differ from those of anaplastic lymphoma kinase (ALK)-rearranged or epidermal growth factor receptor (EGFR)-mutant NSCLC... Conclusion: Although considerable overlap exists in the imaging features of ROS1-rearranged, ALK-rearranged, and EGFR-mutant NSCLC, we found that ROS1-rearranged NSCLC has certain distinct imaging features and patterns of spread. READ ARTICLE

Clinical Lung Cancer DOI:10.1016/j.cllc.2019.10.006

Authors: Subba R. Digumarthy, Dexter P. Mendoza, Jessica J. Lin, Tianqi Chen, Marguerite M. Rooney, Emily Chin, Lecia V. Sequist, Jochen K. Lennerz, Justin F. Gainor, Alice T. Shaw

Real-World OutcomesKirk SmithMarch 1, 2020ALK, Lung cancer, Radiology, Rearrangement, ROS1

Inflammatory myofibroblastic tumor of bone harboring an ALK gene amplification

Inflammatory myofibroblastic tumor (IMT) is a neoplastic proliferation of myofibroblastic/fibroblastic cells with a variable admixture of inflammatory cells. It primarily affects soft tissue and viscera of children and young adults. IMT occurring in bone is extremely rare. Approximately 50% of IMTs carry a clonal rearrangement of the anaplastic lymphoma kinase (ALK) gene, while other receptor tyrosine kinase gene rearrangements have been seen in a small subset of IMT. Herein, we report the first case of IMT which harbors an ALK gene amplification rather than a rearrangement thus resulting in overexpression of the protein, arising from the femur of a 24-year-old man. Our case provides a novel pathogenesis for IMT. An overview of cytogenetic abnormalities of IMT is also integrated into this report. READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2019.152535

Authors: Kai Wang, Rongjun Guo, Gene P. Siegal, Shi Wei