Microsatellites are repeated sequences of DNA. Although the length of these microsatellites is highly variable from person to person, each individual has microsatellites of a set length. These repeated sequences are common, and normal. The most common microsatellite in humans is a dinucleotide repeat of CA, which occurs tens of thousands of times across the genome.
In cells with mutations in DNA repair genes, however, some of these sequences accumulate errors and become longer or shorter. The appearance of abnormally long or short microsatellites in an individual's DNA is referred to as microsatellite instability. Microsatellite instability (MSI) is a condition manifested by damaged DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 due to defects in the normal DNA repair

DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

 process. Sections of DNA called microsatellites, which consist of a sequence

DNA sequence

The sequence or primary structure of a nucleic acid is the composition of atoms that make up the nucleic acid and the chemical bonds that bond those atoms. Because nucleic acids, such as DNA and RNA, are unbranched polymers, this specification is equivalent to specifying the sequence of...

 of repeating units of 1-6 base pair

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s in length, become unstable and can shorten or lengthen. Microsatellites are also known as simple sequence repeats (SSRs).

Clinical significance

MSI is a key factor in several cancers including colorectal, endometrial, ovarian and gastric cancers. Colorectal cancer studies have demonstrated two mechanisms for MSI occurrence.

• The first is in hereditary nonpolyposis colorectal cancer
  Hereditary nonpolyposis colorectal cancer
  Lynch syndrome is an autosomal dominant genetic condition which has a high risk of colon cancer as well as other cancers including endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin...
  
   (HNPCC) or Lynch Syndrome, where an inherited mutation in a mismatch-repair gene causes a microsatellite repeat replication error to go unfixed. Most cases result in changes in the lengths of dinucleotide repeats of the nucleobase
  Nucleobase
  Nucleobases are a group of nitrogen-based molecules that are required to form nucleotides, the basic building blocks of DNA and RNA. Nucleobases provide the molecular structure necessary for the hydrogen bonding of complementary DNA and RNA strands, and are key components in the formation of stable...
  
  s cytosine and adenine (sequence: CACACACACA...). The replication error results in a frameshift mutation that inactivates or alters major tumor suppressor genes - key genes in the regulation of the cell cycle and, ultimately, the prevention of cancer.

• The second mechanism whereby MSI causes colorectal cancer is an epigenetic change that silences an essential mismatch-repair gene.

In both cases, microsatellite insertions and deletions within tumor suppressor gene coding regions result in uncontrolled cell division and tumor growth.

Markers

Five markers have been recommended by the National Cancer Institute to screen for MSI in HNPCC tumors (often called Bethesda markers). Generally, MSI detection in two of the markers is considered a positive result or high probability of MSI (MSI-H).

External links

Software for analyzing AFLP data

• SoftGenetics GeneMarker fragment analysis software