Conservation of mononucleotide repeats within 3 ' and 5 ' untranslated regions and their instability in MSI-H colorectal cancer

Messenger RNA contains untranslated 3' and 5' regions (3' and 5' UTRs) with sequence elements that are essential for the regulation of gene expression . A systematic search of GenBank revealed a large number of mononucleotide repeats within these UTRs. We selected 35 such mononucleotide repeats rangi ng in length from 15 bp to 32 bp and analysed their size in a series of 60 normal individuals. The conservation of repeats correlated inversely to the ir length, with longer repeats generally being more polymorphic than shorte r repeats, irrespective of 3' or 5' location. Several long repeats were ide ntified however to be monomorphic and we postulate that their conservation may be due to selective pressures relating to a possible functional role. W e analysed 19 conserved UTR repeats in 117 colorectal cancers (CRC), 43 of which had defective mismatch repair characterized by widespread microsatell ite instability (MSI-H). The UTR repeats were very often deleted in MSI-H t umors, with the length of deletion being proportional to the size of the re peat. Because of the high frequency of deletion observed in the conserved U TR repeats of MSI-H tumors, these could serve as a useful model for the stu dy of possible changes in gene expression resulting from such mutations.