Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability.
Because the discovery of a link between mismatch repair deficiency and sporadic or inherited human cancers characterized by microsatellite instability (MSI-H tumors), genes containing coding repeat sequences have been found to be mutated at these repeats in MSI-H tumors from different primary sites as reported in the present review. Accumulation of such alterations appears to be the main molecular mechanism by which MSI-H cells accumulate functional changes with putative oncogenic effects. These mutations occur in many genes at variable frequencies. They can affect genes with a putative role in human carcinogenesis involved in different or similar pathways and are thus thought to be inactivating or activating events selected for in these cancers in a recessive or dominant manner. However, because of the high level of instability characterizing these cancers, they are also likely to occur in genes without any expected role in MSI-H carcinogenesis. In light of these recent data, the concept of target genes for instability and their possible role in MSI-H cancers is reconsidered here.
Duval
Alex
A
Institut National de la Santé et de la Recherche Médicale U434: CEPH, 75010 Paris, France.
Hamelin
Richard
R
D020137:Base Pair Mismatch; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*