Spontaneous length variation in microsatellite DNA from human T-cell clones

Abstract

Recently, much interest has been focused on instability of microsatellite DNA sequences such as di- and tri-nucleotide repeats in human cancers. Certain tumors show an increased frequency of mutation leading to repeat length variation at microsatellite loci, and it is thought that such instability may be a marker for the transformed phenotype. However, the spontaneous frequency by which repetitive DNA such as CA-repeats undergoes size changes in normal human somatic cells is not known. Therefore, it is not possible to decide if there is an increase in the frequency of microsatellite mutation in specific tumors or if the change observed simply reflects the frequency of microsatellite mutation in the cell population from which the tumor originates. To investigate this we have established panels of T-lymphocyte clones from 28 healthy males and determined the spontaneous length variations at three CA-repeat markers that are often used to investigate satellite instability: D2S123, D9S180, and D10S197. We found 3 T-cell clones with altered microsatellite size in a total of 178. This corresponds to a background frequency of 3 somatic microsatellite mutations in 1,028 alleles studied, i.e., 2.9 x 10(-3). This frequency is comparable to that found in many tumors of the breast, brain, ovary, and skin but is considerably lower than the frequency of microsatellite mutation in tumors related to hereditary non-polyposis colorectal cancer.