Detection of the Replication Error Phenotype in Ovarian Cancer-PCR Analysis of Microsatellite Instability

Microsatellites are simple, tandemly repeated DNA sequences that are abundantly distributed throughout the human genome, and because of their polymorphic nature have been widely utilized as genetic markers (1). They consist of a repeating unit of 1 to 5 basepairs, averaging 25 to 60 bases in length, and are commonly found in the form d(CA)n: d(GT)n (2). It has been estimated that there are approximately 100,000 CA/GT repeat sequences in the human genome (3). Studies in patients with HNPCC (hereditary nonpolyposis colorectal cancer) first reported the appearance of instability at microsatellites sequences involving either an expansion or contraction of the repeat sequence (4,5). The suggestion that this might reflect a defect in DNA repair was vindicated when subsequent work demonstrated defects in one of four mismatch repair genes [reviewed in (6)]. Such microsatellite instability (MI) has now been reported in a variety of different tumor types including lung, breast, ovary, stomach, endometrium, and bladder [reviewed in (7)].