Copy number variations in DCC/18q and ERBB2/17q are associated with disease-free survival in microsatellite stable colon cancer.

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Date publication

avril 2017

Journal

International journal of cancer

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BOUVIER Anne-Marie, Dr CHAPUSOT Caroline, Pr LEPAGE Côme, Pr MARTIN Laurent


Tous les auteurs :
Sefrioui D, Vermeulin T, Blanchard F, Chapusot C, Beaussire L, Armengol-Debeir L, Sesboué R, Gangloff A, Hebbar M, Copin MC, Houivet E, Schwarz L, Clatot F, Tuech JJ, Bénichou J, Martin L, Bouvier AM, Sabourin JC, Sarafan-Vasseur N, Frébourg T, Lepage C, Michel P, Di Fiore F

Résumé

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.

Mots clés

chromosomal instability, colon cancer, copy number variation, disease-free survival, microstellite stable

Référence

Int. J. Cancer. 2017 Apr;140(7):1653-1661