Genomic context of mutations in MIR142 in blood cancers: summary and integrative analysis

Abstract MIR142 is the most frequently mutated microRNA (miRNA) gene in cancer, with recurrent alterations observed particularly in hematologic malignancies of lymphoid origin. It is expressed at very high levels in blood cells and plays an essential role in the development, differentiation, and maturation of various lymphopoietic and hematopoietic lineages. To gain a deeper understanding of MIR142 mutations, we summarize all data on these mutations, including their frequency in different cancers, their location within the miR-142 precursor, and their functional consequences. We also analyzed MIR142 mutations within a broader genomic context in thousands of cancers, including hundreds of blood neoplasms. Our results show that the most prevalent mutations in the MIR142 gene originate from a clearly distinct hotspot in hematologic malignancies, concentrated mainly within the sequence of the secondary miR-142 precursor. We found substantial differences in mutation frequency and distribution across cancer types. This indicates that MIR142 alterations are not random consequences of an increased mutational load but are likely subject to positive selection, underscoring their biological and clinical significance. Graphical Abstract