title: Genomic index predicts clinical outcome of intermediate-risk gastrointestinal stromal tumours, providing a new inclusion criterion for imatinib adjuvant therapy.
abstract: OBJECTIVE
  Imatinib mesylate is the front-line targeted therapy for gastrointestinal stromal tumours (GISTs). Patient's eligibility to adjuvant imatinib after primary tumour resection is currently based on histological and clinical risk assessment. While therapeutic options are clear for the very-low, low and high-risk subpopulations, no standard is actually available for the tumours classified as intermediate. Since we recently validated genomic index (GI), a measure of the level of genomic alterations, as a strong predictor of clinical outcome in GIST, we asked whether it could also represent a novel prognostic factor for the intermediate subgroup.
  
  
  METHODS
  82 intermediate risk patients were selected based on the Armed Forces Institute of Pathology (AFIP) classification for genomic profiling.
  
  
  RESULTS
  Data revealed that even if studied samples generally harboured a combination of the typical genetic aberrations found in GIST, i.e. 1p, 14q 22q deletions and frequently lost CDKN2A locus on chromosome 9, they profoundly differed from each other on the total number of genomic changes and GI value. Kaplan-Meier analyses of metastatic-free survival unveiled that stratification of the tumours by the GI value at a cutoff of 10 separated the good from the poor prognosis patients, proven that metastatic-risk in GIST intermediate patients is strongly associated with high GI values and genome complexity.
  
  
  CONCLUSIONS
  GI is validated here as a robust marker to predict intermediate-GIST clinical outcome. Applicable in numerous Pathology Laboratories already using array comparative genomic hybridisation (CGH) with formalin-fixed paraffin-embedded (FFPE) samples, this assay presently stands as an efficient tool for the clinical management of intermediate GIST-patients.
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Lartigue
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Neuville
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Lagarde
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Brulard
authors.affiliation: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
authors.affiliation: Department of Anatomic Pathology, Treviso General Hospital, Piazza Ospedale 1, 31100 Treviso, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Dei Tos
authors.affiliation: Universitätsklinikum Münster, Gerhard-Domagk-Institut für Pathologie, Albert-Schweitzer-Campus 1, Gebäude D17, Domagkstraße 17, 48149 Münster, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wardelmann
authors.affiliation: Department of Human Genetics, KU Leuven and University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France; Bordeaux University, 146 rue Léo Saignat, F-33000 Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.affiliation: Department of Biopathology, Bergonie Institute, 229 cours de l'Argonne, F-33076 Bordeaux, France; INSERM U916, 229 cours de l'Argonne, F-33076 Bordeaux, France. Electronic address: f.chibon@bordeaux.unicancer.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chibon
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D009362:Neoplasm Metastasis; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Genomic index; Intermediate-GIST; Metastasis; Miettinen; Prognostic factor