A 'DNA replication' signature of progression and negative outcome in colorectal cancer.
Colorectal cancer is one of the most frequent cancers worldwide. As the tumor-node-metastasis (TNM) staging classification does not allow to predict the survival of patients in many cases, additional prognostic factors are needed to better forecast their outcome. Genes involved in DNA replication may represent an underexplored source of such prognostic markers. Indeed, accidents during DNA replication can trigger 'replicative stress', one of the main features of cancer from earlier stages onward. In this study, we assessed the expression of 47 'DNA replication' genes in primary tumors and adjacent normal tissues from a homogeneous series of 74 patients. We found that genes coding for translesional (TLS) DNA polymerases, initiation of DNA replication, S-phase signaling and protection of replication forks were significantly deregulated in tumors. We also observed that the overexpression of either the MCM7 helicase or the TLS DNA polymerase POLQ (if also associated with a concomitant overexpression of firing genes) was significantly related to poor patient survival. Our data suggest the existence of a 'DNA replication signature' that might represent a source of new prognostic markers. Such a signature could help in understanding the molecular mechanisms underlying tumor progression in colorectal cancer patients.
Pillaire
M-J
MJ
Genetic Instability and Cancer Group, Department Biology of Cancer, Institute of Pharmacology and Structural Biology, UMR5089 CNRS, University of Toulouse, University Paul Sabatier, Toulouse, France.
Selves
J
J
Gordien
K
K
Gourraud
P-A
PA
Gouraud
P-A
PA
Gentil
C
C
Danjoux
M
M
Do
C
C
Negre
V
V
Bieth
A
A
Guimbaud
R
R
Trouche
D
D
Pasero
P
P
Méchali
M
M
Hoffmann
J-S
JS
Cazaux
C
C
D018797:Cell Cycle Proteins / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D064168:Minichromosome Maintenance Complex Component 7; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D000097462:DNA Polymerase theta
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins; D000097462:DNA Polymerase theta; C101624:MCM7 protein, human