L'instabilité des microsatellites dans les cancers du côlon

Characteristics of microsatellites instability (MSI) is abnormal variation of the number of repeated sequences in DNA from the tumor compared to DNA of healthy tissue from the same individual. MSI has been first described in a rare hereditary colon cancer Lynch syndrome or HNPCC syndrome (hereditary nonpolyposis colon cancer) caused by MMR (mismatch repair) genes defects. Later, MSI was described in 15% of sporadic colon cancer. To confirm the diagnosis of MSI, a panel of five markers are used, amplified by multiplex PCR. MSI associated with clinical criteria (Amsterdam or Bethesda criteria) are recommended for MMR genes molecular testing to confirm HNPCC. Genetic counselling, familial investigation and possibly prophylactic measures are then taken. In sporadic cancers, MSI is the consequence of MLH1 silencing by epimutation in the promotor and is correlated with a better prognosis and maybe a resistance to fluorouracile, an adjuvant chemotherapy of colon cancer.