Replication error (RER) is defined as mutation events in
repetitive DNA segments. To investigate
further the RER phenomenon and reveal any differences in mutation outcome
between different
short tandem repeat (STR) loci, we have investigated the somatic mutation
rate and the size
distribution of new tumour alleles in four tetranucleotide STRs
in a large material of unselected
colorectal adenocarcinomas. DNA was extracted from the blood and
carcinomas of 217 patients. All
blood/tumour pairs were analysed using the STRs HUMTHO1, HUMFES/FPS,
HUMVWA31/A
and HUMF13A1. Mutations are detected at all four loci. There are substantial
differences in
mutation rate and mutation direction (i.e. expansion versus
contraction) between different STR loci.
In all four STRs, the majority of events represent gain or loss of a
single repeat. Almost all new
tumour alleles correspond to known alleles in a population database,
indicating that these are also
composed of integers of the four base pair repeat. There is no statistically
significant size bias in the
mutating alleles as compared to the allelic distribution in the population
database.