title: Stabilization of disease after targeted therapy in a thymic carcinoma with KIT mutation detected by clinical next-generation sequencing.
abstract: Precision medicine uses individually determined genomic information to guide treatment in cancer and other diseases. We have implemented a clinical genomics assay that uses targeted next-generation sequencing of 25 cancer-related genes to guide the use of targeted therapies in diverse malignancies. We report the case of a 55-year-old woman with a poorly differentiated squamous cell carcinoma of thymic origin, with disease progression after standard treatment. Targeted tumor sequencing revealed the presence of a KIT codon 579 deletion (p.D579del). This specific mutation has not previously been associated with thymic tumors, but has been reported in gastrointestinal stromal tumors and has been associated with response to imatinib. Imatinib therapy was instituted for and resulted in stabilization of disease. This case illustrates the potential of clinical next-generation sequencing to open unexpected avenues for treatment and thereby improve patient outcomes.
authors.affiliation: *Genomics and Pathology Services, Department of Pathology and Immunology, †Section of Medical Oncology, Department of Medicine, and ‡Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Hagemann
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Cylen
authors.initials: C
authors.lastname: Javidan-Nejad
authors.forename: John D
authors.initials: JD
authors.lastname: Pfeifer
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Cottrell
mesh_terms: D000369:Aged, 80 and over; D001549:Benzamides / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D000068877:Imatinib Mesylate; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D013953:Thymus Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit