Differential rates of frameshift alterations in four repeat sequences of XXXX .

@entity1 @entity6756 @entity589 @entity2534 @entity5 @entity14 @entity9302
DNA sequences of mono-, di-, and trinucleotide repeats are prone to replication errors and thus constitute mutational hot spots. This is well illustrated by the occurrence of DNA microsatellite instability in @entity5 from @entity1 affected by @entity14 ( @entity14 ) resulting from a defect in a gene that participates in postreplicative DNA mismatch repair (MMR). We selected repeat sequences present within coding regions of four genes involved in either cell proliferation or promotion of apoptosis. These repeats consisted of (A)10 in the @entity2534 , (G)8 in the @entity589 , (A)8 in the @entity9302 , and (CCA)7 in the APP genes. These repeats were analyzed in ten @entity5 from @entity14 @entity1 carrying a germline pathogenic mutation in the MMR gene @entity6756 . For each @entity5 the rate of somatic replication errors was measured by sequencing 20-50 cloned PCR-amplified fragments. Substantial intertumor variations were observed in the pattern of repeat alterations, with error rates varying between 12% and 80% for @entity2534 , 2% and 84% for @entity589 , 0% and 30% for @entity9302 , and 0% to 18% for APP. The @entity589 repeat error rate did not exceed 20% in nine of the ten @entity5 , in contrast to results from previous studies. High error rates in more than one gene in a same @entity5 suggested additive selective effects from inactivation of different pathways influencing tumorigenesis. Our methodology can contribute to define @entity5 characteristics and may, if applied to genes strongly involved in tumorigenesis, improve @entity5 classification and outcome prediction.
