Novel Mutations in a Patient with ALK-Rearranged Lung Cancer

• Published in: The New England journal of medicine Vol. 371; no. 17; pp. 1655 - 1656
• Main Authors: Giri, Smith, Patel, Jashmin K, Mahadevan, Daruka
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 23.10.2014
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Antineoplastic Agents - therapeutic use; Cell cycle; Drug resistance; Drug Resistance, Neoplasm - genetics; Female; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Middle Aged; Mutation; Pyrazoles - therapeutic use; Pyridines - therapeutic use; Receptor Protein-Tyrosine Kinases - genetics; Signal transduction; Translocation, Genetic
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMc1410799

A variety of mechanisms of crizotinib resistance have been defined in patients with ALK -rearranged lung cancer who no longer have a response to the drug. A case is presented in which the tumor lost the rearrangement and mutations developed in several other genes. To the Editor: A 49-year-old nonsmoking woman presented with pleuritic pain on the right side of her chest. Computed tomography (CT) of the chest revealed a spiculated, noncalcified pulmonary nodule in the right middle lobe 1.2 cm in diameter and multiple noncalcified nodules (2.0 to 3.0 mm in diameter) in the right middle lobe and right lower lobe. A positron-emission tomographic (PET) scan showed the nodule in the right middle lobe and multiple hypermetabolic foci in the right diaphragmatic pleura indicative of metastatic disease (stage IV). A surgical biopsy confirmed a moderately differentiated adenocarcinoma. Molecular analysis revealed an EML4-ALK translocation . . .