title: STUMP un"stumped": anti-tumor response to anaplastic lymphoma kinase (ALK) inhibitor based targeted therapy in uterine inflammatory myofibroblastic tumor with myxoid features harboring DCTN1-ALK fusion.
abstract: BACKGROUND
  Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein.
  
  
  METHODS
  Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ).
  
  
  RESULTS
  Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria.
  
  
  CONCLUSIONS
  For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. vsubbiah@mdanderson.org.
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. cmcmahon@foundationmedicine.com.
authors.forename: Caitlin
authors.initials: C
authors.lastname: McMahon
authors.affiliation: Division of Cancer Medicine, Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. spatel@mdanderson.org.
authors.forename: Shreyaskumar
authors.initials: S
authors.lastname: Patel
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. rzinner@mdanderson.org.
authors.forename: Ralph
authors.initials: R
authors.lastname: Zinner
authors.affiliation: Division of Diagnostic Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. esilva@mdanderson.org.
authors.forename: Elvio G
authors.initials: EG
authors.lastname: Silva
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jelvin@foundationmedicine.com.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. ISubbiah@mdanderson.org.
authors.forename: Ishwaria M
authors.initials: IM
authors.lastname: Subbiah
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. COhaji@mdanderson.org.
authors.forename: Chimela
authors.initials: C
authors.lastname: Ohaji
authors.affiliation: Division of Diagnostic Imaging and Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. DGaneshan@mdanderson.org.
authors.forename: Dhakshina Moorthy
authors.initials: DM
authors.lastname: Ganeshan
authors.affiliation: Division of Diagnostic Imaging and Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA. Adeepa003@gmail.com.
authors.forename: Deepa
authors.initials: D
authors.lastname: Anand
authors.affiliation: Division of Surgery, Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. clevenba@mdanderson.org.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Levenback
authors.affiliation: Division of Cancer Medicine, Department of Investigational Cancer Therapeutic (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, FC8.3038, Box 0455, Houston, TX, 77030, USA. JRBerry@mdanderson.org.
authors.forename: Jenny
authors.initials: J
authors.lastname: Berry
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. tibrennan@foundationmedicine.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Brennan
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jchmielecki@foundationmedicine.com.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. zchalmers@foundationmedicine.com.
authors.forename: Zachary R
authors.initials: ZR
authors.lastname: Chalmers
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. jmayfield@foundationmedicine.com.
authors.forename: John
authors.initials: J
authors.lastname: Mayfield
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. vmiller@foundationmedicine.com.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. pstephens@foundationmedicine.com.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. rossj@mail.amc.edu.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Foundation Medicine, Inc, Cambridge, MA, 02141, USA. sali@foundationmedicine.com.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D050939:Gene Fusion / Q000235:genetics*; D023281:Genomics; D006801:Humans; D008637:Mesenchymoma / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases