Spotlight on MSI Colon Cancer

Historically, cancers have been classified by their location (colon, lung, skin, etc) and their outward appearance. In reality, the “same” cancer is really different cancers depending on the actual cause of the abnormal growth and knowing this cause helps with the treatment and the screening protocols.

Colon cancers with microstatellite instability (MSI) account for 10–15% of all colon cancers and have a very different origin then the majority of colon cancers (called MSS: “microsatellite stable”). MSI colon cancer starts with a malfunctioning mismatch repair (MMR) gene. The genetic code is a long sequence of four letters (ACGT) that carry the instructions on how a cell should operate. Each gene is divided into three major parts.

The “left part” is called the 5'UTR (untranslated region), the middle part is the coding sequence, and the right part is called the 3'UTR. Each part plays an important role in insuring that the cells function properly. We can view the “coding sequence” as having the recipe information and the left and right side serving supporting roles.

In each of the three parts, the core information is stored as a sequence of letters from the four letter alphabet (ACGT are the four letters). For example, one part of the code might be the sequence “ACCGCTAAAAAAATCGAGG”. Since cells are always reproducing, this code is always being copied or replicated. Like any “copying mechanism,” mistakes can be made.

For example, the copying mechanism might drop one of the A’s in the long “repeat” sequence of A’s. The copy might be “ACCGCTAAAAAATCGAGG” (there are only six A’s in this copy as opposed to seven A’s in the original). The MMR gene checks the copy for errors and corrects them if an error is found. As you might imagine, the failure to catch and correct such errors can be a problem. In the example given above, the failure to catch the error results in the “repeat sequence of A’s” being shortened from seven to six— this is called microsatellite instability.

Mismatch Repair Failure Leads to Microsatellite Instability (MSI)