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Copy number variations in DCC/ 18q and ERBB2/ 17q are associated with disease‐free survival in microsatellite stable colon cancer
Author(s) -
Sefrioui David,
Vermeulin Thomas,
Blanchard France,
Chapusot Caroline,
Beaussire Ludivine,
ArmengolDebeir Laura,
Sesboué Richard,
Gangloff Alice,
Hebbar Mohamed,
Copin MarieChristine,
Houivet Estelle,
Schwarz Lilian,
Clatot Florian,
Tuech JeanJacques,
Bénichou Jacques,
Martin Laurent,
Bouvier AnneMarie,
Sabourin JeanChristophe,
SarafanVasseur Nasrin,
Frébourg Thierry,
Lepage Côme,
Michel Pierre,
Di Fiore Frédéric
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30584
Subject(s) - copy number variation , colorectal cancer , hazard ratio , biology , medicine , oncology , cancer , multiplex , confidence interval , genetics , gene , genome
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.