title: Somatic mutational spectrum analysis in a prospective series of 104 gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besançon between August 2005 and October 2014 were prospectively included in the present study. KIT, PDGFRA and KRAS-codons 12 and 13 as well as BRAF codon 600 mutations were analyzed by Sanger sequencing or SNaPshot. KIT and PDGFRA mutations were detected in 71.2 and 19.2% of the cases, respectively. A total of 43 different mutations were detected of which 13 had never been described. As expected, KIT exon 9 and PDGFRA exon 18 mutations were associated with small bowel and gastric localizations respectively. No mutation was found in KRAS and BRAF. Molecular studies are critical to improve the management of GISTs. Our study enhances the current knowledge by describing 13 new mutations in KIT. A common molecular pattern in all KIT exon 11 substitutions is also described for the first time in this study but its significance remains unknown since genetic and environmental risk factors favoring the development of GISTs such as DNA repair defects and exposure to carcinogens are not currently known.
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: David
authors.initials: D
authors.lastname: Guenat
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Deroo
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Magnin
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Chaigneau
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Monnien
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mougin
authors.affiliation: Université Versailles, Boulogne, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.affiliation: CHRU Besançon, Besançon, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Prétet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016283:Proto-Oncogene Proteins p21(ras)