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 ranging 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 their length, with longer repeats generally being more polymorphic than shorter repeats, irrespective of 3' or 5' location. Several long repeats were identified however to be monomorphic and we postulate that their conservation may be due to selective pressures relating to a possible functional role. We analysed 19 conserved UTR repeats in 117 colorectal cancers (CRC), 43 of which had defective mismatch repair characterized by widespread microsatellite instability (MSI-H). The UTR repeats were very often deleted in MSI-H tumors, with the length of deletion being proportional to the size of the repeat. Because of the high frequency of deletion observed in the conserved UTR repeats of MSI-H tumors, these could serve as a useful model for the study of possible changes in gene expression resulting from such mutations.
Suraweera
N
N
INSERM U434, CEPH, 27 rue Juliette Dodu, 75010 Paris, France.
Iacopetta
B
B
Duval
A
A
Compoint
A
A
Tubacher
E
E
Hamelin
R
R
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D015179:Colorectal Neoplasms / Q000235:genetics*; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats / Q000235:genetics*; D010641:Phenotype; D012091:Repetitive Sequences, Nucleic Acid
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018076:DNA, Complementary; D004247:DNA