[Clinical and molecular consequences of microsatellite instability in human cancers].
During each cell division, DNA polymerase makes mistakes while copying DNA. These errors, more frequent at the level of repeated sequences called microsatellites are normally repaired by a system called MMR (mismatch repair). Tumors defective in their MMR system accumulate mutations (deletions and insertions of some nucleotides) at the level of microsatellites and are called MSI (microsatellite instability). Microsatellites are numerous and scattered throughout the genome, in coding and non-coding regions. The instability of non-coding microsatellites is not known to have a major role in the process of cell transformation, but is a good indicator of the MSI status. On the other hand, instability by deletion or insertion in a coding region leads to a frameshift within the gene containing the repeat. The consequence is, the more often, the inactivation of this gene that potentially plays a role in initiation and/or MSI tumor progression. The MSI phenotype was first described in about 15 % of colorectal cancers that maybe of sporadic or hereditary (Lynch syndrome, or HNPCC for hereditary non-polyposis colorectal cancer) origin. It is also associated with about 15 % of gastric and endometrial tumors, and to a lesser extent with other human tumors. Besides a fundamental interest because of its original transformation mechanism, the analysis of MSI tumors is also important for clinical reasons. It was indeed shown that MSI tumors were associated with a better prognosis than non-MSI (also called MSS for microsatellite stable) tumors, and responded differently to conventional chemotherapeutic drugs used for the management of colorectal cancers. All these points will be discussed in details in the present review.
Hamelin
Richard
R
Inserm, UMRS 762, 27 rue Juliette Dodu, 75010 Paris, France. richard.hamelin@cephb.fr
Chalastanis
Alexandra
A
Colas
Chrystelle
C
El Bchiri
Jamila
J
Mercier
Dominique
D
Schreurs
Ann-Sofie
AS
Simon
Virginie
V
Svrcek
Magali
M
Zaanan
Aziz
A
Borie
Claire
C
Buhard
Olivier
O
Capel
Emilie
E
Zouali
Habib
H
Praz
Françoise
F
Muleris
Martine
M
Fléjou
Jean-François
JF
Duval
Alex
A
D020137:Base Pair Mismatch / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000188:drug therapy / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D015925:Cryopreservation / Q000379:methods; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D020871:RNA Stability; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics; D016707:Tissue Fixation / Q000379:methods