title: Identification of I1171N resistance mutation in ALK-positive non-small-cell lung cancer tumor sample and circulating tumor DNA.
abstract: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitor therapy, but resistance invariably develops and can be mediated by certain secondary mutations. The detection of these mutations is useful to guide treatment decisions, but tumors are not always easily accessible to re-biopsy. We report the case of a patient with ALK-rearranged NSCLC who presented acquired resistance to crizotinib and then alectinib. Sequencing analyses of DNA from a liver metastasis biopsy sample and circulating tumor DNA both found the same I1171N ALK kinase domain mutation, known to confer resistance to certain ALK inhibitors. However, the patient then received ceritinib, a 2nd generation ALK inhibitor, and achieved another partial response. This case underlines how ALK resistance mutation detection in peripheral blood could be a reliable, safer, and less invasive alternative to tissue-based samples in NSCLC.
authors: Department of Oncology, Centre François Baclesse, 14000 Caen, France. Electronic address: acj.france@gmail.com.
authors: Alison C
authors: AC
authors: Johnson
authors: Department of Oncology, Centre François Baclesse, 14000 Caen, France.
authors: Pascal
authors: P
authors: Dô
authors: Department of Genetics, Centre Hospitalier Universitaire de Caen, 14000 Caen, France.
authors: Nicolas
authors: N
authors: Richard
authors: Department of Oncology, Centre François Baclesse, 14000 Caen, France.
authors: Catherine
authors: C
authors: Dubos
authors: Department of Pathology, Centre François Baclesse, 14000 Caen, France.
authors: Jean Jacques
authors: JJ
authors: Michels
authors: GENECAN Platform, Centre Hospitalier Universitaire de Caen, 14000 Caen, France.
authors: Jessica
authors: J
authors: Bonneau
authors: Department of Oncology, Centre François Baclesse, 14000 Caen, France.
authors: Radj
authors: R
authors: Gervais
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000074141:Circulating Tumor DNA; D003062:Codon; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014057:Tomography, X-Ray Computed
chemical_list: D000970:Antineoplastic Agents; D000074141:Circulating Tumor DNA; D003062:Codon; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; Circulating tumor DNA; Crizotinib; Non-small cell lung cancer; Resistance mutation