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 [CHU Lille]
8 Service de pathologie [CHU Lille]
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]

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.

Domaines: Sciences du Vivant [q-bio]

David Sefrioui, Thomas Vermeulin, France Blanchard, Caroline Chapusot, Ludivine Beaussire, et al.. Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease-free survival in microsatellite stable colon cancer. International Journal of Cancer, 2017, 140 (7), pp.1653-1661. ⟨10.1002/ijc.30584⟩. ⟨hal-02353187⟩