Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer
David Sefrioui
(1, 2)
,
Thomas Vermeulin
(3)
,
France Blanchard
(4, 2)
,
Caroline Chapusot
(5)
,
Ludivine Beaussire
(2)
,
Laura Armengol-Debeir
(6)
,
Richard Sesboüé
(1, 2)
,
Alice Gangloff
(6, 2)
,
Mohamed Hebbar
(7)
,
Marie-Christine Copin
(8)
,
Estelle Houivet
(9)
,
Lilian Schwarz
(10)
,
Florian Clatot
(11, 2)
,
Jean-Jacques Tuech
(10, 2)
,
Jacques Bénichou
(12)
,
Laurent Martin
(13)
,
Anne-Marie Bouvier
(5)
,
Jean-Christophe Sabourin
(14, 2)
,
Nasrin Sarafan-Vasseur
(1, 2)
,
Thierry Frébourg
(2)
,
Côme Lepage
(5)
,
Pierre Michel
(2)
,
Frédéric Di Fiore
(15, 2)
1
GMFC -
Génétique du cancer et des maladies neuropsychiatriques
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 Hôpital Charles Nicolle [Tunis]
4 Service de génétique [Rouen]
5 LNC - Lipides - Nutrition - Cancer (U866)
6 Service d'Hépato-Gastroentérologie [CHU Rouen]
7 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
8 Service de Pathologie
9 CHU Rouen
10 Hôpital Charles Nicolle [Rouen]
11 GPL - Groupe d'étude des proliférations lymphoïdes
12 Unité de biostatistiques [CHU Rouen]
13 Centre Guillaume le Conquérant
14 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
15 Département d'oncologie médicale [Rouen]
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 Hôpital Charles Nicolle [Tunis]
4 Service de génétique [Rouen]
5 LNC - Lipides - Nutrition - Cancer (U866)
6 Service d'Hépato-Gastroentérologie [CHU Rouen]
7 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
8 Service de Pathologie
9 CHU Rouen
10 Hôpital Charles Nicolle [Rouen]
11 GPL - Groupe d'étude des proliférations lymphoïdes
12 Unité de biostatistiques [CHU Rouen]
13 Centre Guillaume le Conquérant
14 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
15 Département d'oncologie médicale [Rouen]
David Sefrioui
- Function : Author
- PersonId : 940307
France Blanchard
- Function : Author
- PersonId : 940311
Richard Sesboüé
- Function : Author
- PersonId : 940319
Marie-Christine Copin
- Function : Author
- PersonId : 752195
- IdHAL : marie-christine-copin
- ORCID : 0000-0002-4729-7054
- IdRef : 081784465
Florian Clatot
- Function : Author
- PersonId : 179014
- IdHAL : florian-clatot
- ORCID : 0000-0002-7074-9282
- IdRef : 144792532
Nasrin Sarafan-Vasseur
- Function : Author
- PersonId : 179351
- IdHAL : nasrin-vasseur
- IdRef : 180744178
Thierry Frébourg
- Function : Author
- PersonId : 902596
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 vs 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. This article is protected by copyright. All rights reserved.