title: Detection of a TRAF1-ALK fusion in an anaplastic large cell lymphoma patient with chemotherapy and ALK inhibitor-resistant disease.
abstract: BACKGROUND
  The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, which was first identified as the fusion partner of the nucleophosmin (NPM1) gene in the recurrent t(2;5)(p23;q35) found in a subset of anaplastic large cell lymphoma (ALCL). Several distinct, non-NPM1, ALK fusions have subsequently been described in lymphomas and other tumor types. All of these fusions result in the constitutive expression and activation of ALK and ALK signaling pathways, ultimately leading to the malignant phenotype.
  
  
  METHODS
  A non-NPM1 fusion partner of ALK was identified in a 32-year-old Caucasian male ALCL patient whose disease was refractory to standard chemotherapy and autologous stem cell transplantation, and exhibited a poor response to a first-generation ALK inhibitor. Non-allele-specific ALK RT-qPCR revealed ALK overexpression and 5' RACE PCR revealed that the patient's lymphoma expressed a TRAF1-ALK fusion.
  
  
  CONCLUSIONS
  We report the case of an ALCL patient whose tumor harbored the newly recognized TRAF1-ALK fusion and describe the clinical outcome after treatment with an ALK inhibitor. The short survival of our patient may reflect a propensity toward aggressive behavior in lymphomas that express this ALK fusion.
authors.affiliation: Insight Genetics, Suite 510, 2 International Plaza, Nashville, TN, 37217, USA. klawrence@insightgenetics.com.
authors.forename: Kasey
authors.initials: K
authors.lastname: Lawrence
authors.affiliation: Department of Pathology, Royal Jubilee Hospital, 1952 Bay Street, Victoria, BC, V8R 1J8, Canada. brian.berry@viha.ca.
authors.forename: Brian
authors.initials: B
authors.lastname: Berry
authors.affiliation: Insight Genetics, Suite 510, 2 International Plaza, Nashville, TN, 37217, USA. jhandshoe@insightgenetics.com.
authors.forename: John
authors.initials: J
authors.lastname: Handshoe
authors.affiliation: Insight Genetics, Suite 510, 2 International Plaza, Nashville, TN, 37217, USA. dhout@insightgenetics.com.
authors.forename: David
authors.initials: D
authors.lastname: Hout
authors.affiliation: British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC, V8R 6V5, Canada. rosetta.mazzola@bccancer.bc.ca.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Mazzola
authors.affiliation: Insight Genetics, Suite 510, 2 International Plaza, Nashville, TN, 37217, USA. smorris@insightgenetics.com.
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Morris
authors.affiliation: British Columbia Cancer Agency, 2410 Lee Avenue, Victoria, BC, V8R 6V5, Canada. David.saltman@bccancer.bc.ca.
authors.forename: David L
authors.initials: DL
authors.lastname: Saltman
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D017809:Fatal Outcome; D015870:Gene Expression; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008297:Male; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*; D014182:Transplantation, Autologous
chemical_list: D000970:Antineoplastic Agents; C000716967:NPM1 protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D047990:TNF Receptor-Associated Factor 1; D000090243:Nucleophosmin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases