title: Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: A new mechanism of resistance to ALK inhibitors.
abstract: Various mechanisms of resistance to ALK inhibitors in ALK rearranged adenocarcinomas are reported including secondary gatekeeper mutations, bypass signaling or ALK amplifications as the commonest ones. We report a new mechanism of resistance with transformation of adenocarcinoma into small cell lung cancer. A 53-year-old non-smoker woman, experienced cancer progression after two lines of ALK inhibitors. A new biopsy showed a small cell lung cancer. FISH revealed persistent ALK rearrangement with an atypical pattern and complete loss of the 5' region of the ALK gene.
authors.affiliation: Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Levacq
authors.affiliation: Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Nicky
authors.initials: N
authors.lastname: D'Haene
authors.affiliation: Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Roland
authors.initials: R
authors.lastname: de Wind
authors.affiliation: Department of Pathology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Remmelink
authors.affiliation: Department of Intensive Care and Oncological Emergencies & Thoracic Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: thierry.berghmans@bordet.be.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berghmans
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D000072078:Positron Emission Tomography Computed Tomography; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015898:Tomography Scanners, X-Ray Computed; D014178:Translocation, Genetic
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK translocation; Lung neoplasms; Small cell cancer transformation