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Spliceosome mutations in hematopoietic malignancies

Nature Genetics volume 44, pages 9–10 (2012)Cite this article

Recent studies, including two in this issue, report heterozygous missense mutations in the U2AF1 and SF3B1 genes that encode spliceosome subunits. U2AF1 is frequently mutated in myeloid hematopoietic malignancies, especially in myelodysplastic syndrome (MDS), and SF3B1 is frequently mutated in both MDS and chronic lymphocytic leukemia (CLL).

Introns in protein-encoding genes are removed by spliceosomes in the nucleus, which are complexes composed of small nuclear RNA (snRNA) and numerous protein subunits. Eukaryotic genomes contain two types of introns, U2, which contain highly conserved dinucleotides at their termini (5′-GT and 3′-AG), and the rare U12 type, with distinct sequence elements that are present in only ∼600 mammalian genes. Alternative splicing, including tissue-specific splicing, can generate numerous transcript variants for each gene, and RNA molecules derived from introns as well as the presence of introns within transcripts may have regulatory roles in the genome. Thus, alternative splicing clearly adds to genomic complexity and, thus, evolutionary potential, including under the selective conditions that may occur in cancer. Evidence of cancer-specific alternative splicing and oncogenic somatic mutations in spliceosome subunits has been steadily growing, but now the floodgates have opened.

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Figure 1: Alterations in the SF3B1 and U2AF1 splicing factors in MDS, CLL and other cancers.

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  1. Christopher N. Hahn and Hamish S. Scott are in the Department of Molecular Pathology at the Centre for Cancer Biology at SA Pathology in Adelaide, Australia.,

    Christopher N Hahn & Hamish S Scott

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  1. Christopher N Hahn
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  2. Hamish S Scott
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Correspondence to Christopher N Hahn or Hamish S Scott.

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Hahn, C., Scott, H. Spliceosome mutations in hematopoietic malignancies. Nat Genet 44, 9–10 (2012). https://doi.org/10.1038/ng.1045

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