title: Impact of KIT exon 10 M541L allelic variant on the response to imatinib in aggressive fibromatosis: analysis of the desminib series by competitive allele specific Taqman PCR technology.
abstract: BACKGROUND
  Aggressive fibromatosis (AF) is a rare fibroblastic proliferative disease with a locally aggressive behavior and no distant metastasis, characterized by driver mutations in CTNNB1 or the APC gene. When progressive and/or symptomatic AF is not amenable to local management, a variety of medical treatments may be efficient, including imatinib mesylate. The phase II "Desminib trial" included 40 patients with AF to evaluate the toxicity and efficacy of imatinib resulting in a 65% tumor control rate at 1 year. We investigated a potential predictive value of KIT exon 10 M541L variant (KITL541) on this prospective series.
  
  
  METHODS
  DNA was extracted in sufficient quantity from 33 patients included in the Desminib trial. The detection of KITL541 was performed by Competitive Allele-Specific Taqman® PCR technology. Chi-2 analyses were performed to search for a correlation between KIT status and tumor response. Progression free (PFS) and overall survival (OS) were compared by log-rank test after Kaplan-Meier analysis.
  
  
  RESULTS
  In 6 out of 33 cases (18%), the technique failed to determine the mutational status; 5 patients (19%) harboured KITL541 and 22 patients (81%) were classified as KIT wild type. Compared with total cohort, KITL541 frequency did not distinguish between different clinical characteristics. In the KITL541 and the KITWT subgroups, the tumor control rate at 1 year was 100% and 68%, respectively (p = 0.316). The median PFS of patients harboring KITL541 or not is 29.9 and 24.5 months, respectively (p = 0.616), and the median OS is not reached, in any of the groups.
  
  
  CONCLUSIONS
  Our results do not support a predictive effect of KITL541 on the efficacy of imatinib for patients with AF.
authors.affiliation: Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Leon Berard, 28 rue Laënnec, Lyon, France. a.dufresne@hotmail.com.
authors.forename: Armelle
authors.initials: A
authors.lastname: Dufresne
authors.forename: Laurent
authors.initials: L
authors.lastname: Alberti
authors.forename: Mehdi
authors.initials: M
authors.lastname: Brahmi
authors.forename: Sarah
authors.initials: S
authors.lastname: Kabani
authors.forename: Héloïse
authors.initials: H
authors.lastname: Philippon
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Jean Yves
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000008:administration & dosage* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D018222:Desmoid Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014644:Genetic Variation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction / Q000379:methods*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit