title: Copy number variations in DCC/18q and ERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer.
abstract: We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II-III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end-point was the impact of the CNVs on the 4-year disease-free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4-year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5-4.1) and 3.1 (95% CI, 1.2-8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II-III MSS colon cancer.
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.|Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.
authors.forename: David
authors.initials: D
authors.lastname: Sefrioui
authors.affiliation: Department of Biostatistics, Rouen University Hospital, Rouen, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vermeulin
authors.affiliation: EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.|Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: France
authors.initials: F
authors.lastname: Blanchard
authors.affiliation: Department of Pathology, Dijon University Hospital, University of Burgundy, Dijon, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chapusot
authors.affiliation: Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Beaussire
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Armengol-Debeir
authors.affiliation: Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Sesboué
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.|Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Gangloff
authors.affiliation: Department of Medical Oncology, Lille University Hospital, Lille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.affiliation: Department of Pathology, Lille University Hospital, Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.affiliation: Department of Biostatistics, Rouen University Hospital, Rouen, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Houivet
authors.affiliation: Department of Surgery, Rouen University Hospital, Rouen, France.
authors.forename: Lilian
authors.initials: L
authors.lastname: Schwarz
authors.affiliation: Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Clatot
authors.affiliation: Department of Surgery, Rouen University Hospital, Rouen, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Tuech
authors.affiliation: Department of Biostatistics, Rouen University Hospital, Rouen, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Bénichou
authors.affiliation: Department of Pathology, Dijon University Hospital, University of Burgundy, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.affiliation: Digestive Cancer Registry of Burgundy, INSERM U866, University Hospital Dijon, University of Burgundy, Dijon, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bouvier
authors.affiliation: Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.|Department of Pathology, Rouen University Hospital, Rouen, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Sarafan-Vasseur
authors.affiliation: Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.affiliation: Digestive Cancer Registry of Burgundy, INSERM U866, University Hospital Dijon, University of Burgundy, Dijon, France.
authors.forename: Côme
authors.initials: C
authors.lastname: Lepage
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.|Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.affiliation: Digestive Oncology Unit, Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France.|Inserm U1079, University of Rouen, Institute for Biomedical Research and Innovation, Rouen, France.|EquIpe de Recherche en ONcogie (IRON), Rouen University Hospital, Rouen, France.|Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Di Fiore
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000075389:DCC Receptor; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000075389:DCC Receptor; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C501909:DCC protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human
keywords: chromosomal instability; colon cancer; copy number variation; disease-free survival; microstellite stable