Micro RNA ‐142 is mutated in about 20% of diffuse large B ‐cell lymphoma

Micro RNA s ( miRNA s) are short 18–23 nucleotide long noncoding RNA s that posttranscriptionally regulate gene expression by binding to mRNA . Our previous miRNA profiling of diffuse large B ‐cell lymphoma ( DLBCL ) revealed a mutation in the seed sequence of miR‐142‐3p. Further analysis now showed that miR‐142 was mutated in 11 (19.64%) of the 56 DLBCL cases. Of these, one case had a mutation in both alleles, with the remainder being heterozygous. Four mutations were found in the mature miR‐142‐5p, four in the mature miR‐142‐3p, and three mutations affected the miR‐142 precursor. Two mutations in the seed sequence redirected miR‐142‐3p to the mRNA of the transcriptional repressor ZEB 2 and one of them also targeted the ZEB 1 mRNA . However, the other mutations in the mature miR‐142‐3p did not influence either the ZEB 1 or ZEB 2 3′ untranslated region (3′ UTR ). On the other hand, the mutations affecting the seed sequence of miR‐142‐3p resulted in a loss of responsiveness in the 3′ UTR of the known miR‐142‐3p targets RAC 1 and ADCY 9. In contrast to the mouse p300 gene, the human p300 gene was not found to be a target for miR‐142‐5p. In one case with a mutation of the precursor, we observed aberrant processing of the miR‐142‐5p. Our data suggest that the mutations in miR‐142 probably lead to a loss rather than a gain of function. This is the first report describing mutations of a miRNA gene in a large percentage of a distinct lymphoma subtype.