Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML

Shinsuke Hirabayashi, Christian Flotho, Jessica Moetter, Michael Heuser, Henrik Hasle, Bernd Gruhn, Thomas Klingebiel, Felicitas Thol, Brigitte Schlegelberger, Irith Baumann, Brigitte Strahm, Jan Stary, Franco Locatelli, Marco Zecca, Eva Bergstraesser, Michael Dworzak, Marry M. Van Den Heuvel-Eibrink, Barbara De Moerloose, Seishi Ogawa, Charlotte M. NiemeyerMarcin W. Wlodarski

Research output: Contribution to journalArticle

Abstract

Somatic mutations of the spliceosomal machinery occur frequently in adult patients with myelodysplastic syndrome (MDS). We resequenced SF3B1, U2AF35, and SRSF2 in 371 children with MDS or juvenile myelomonocytic leukemia. We found missense mutations in 2 juvenile myelomonocytic leukemia cases and in 1 child with systemic mastocytosis with MDS. In 1 juvenile myelomonocytic leukemia patient, the SRSF2 mutation that initially coexisted with an oncogenic NRAS mutation was absent at relapse, whereas the NRAS mutation persisted and a second, concomitant NRAS mutation later emerged. The patient with systemic mastocytosis and MDS carried both mutated U2AF35 and KIT in a single clone as confirmed by clonal sequencing. In the adult MDS patients sequenced for control purposes, we detected previously reported mutations in 7/30 and a novel SRSF2 deletion (c.284-307del) in 3 of 30 patients. These findings implicate that spliceosome mutations are rare in pediatric MDS and juvenile myelomonocytic leukemia and are unlikely to operate as driver mutations.

Original languageEnglish
JournalBlood
Volume119
Issue number11
DOIs
Publication statusPublished - Mar 15 2012

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Hirabayashi, S., Flotho, C., Moetter, J., Heuser, M., Hasle, H., Gruhn, B., Klingebiel, T., Thol, F., Schlegelberger, B., Baumann, I., Strahm, B., Stary, J., Locatelli, F., Zecca, M., Bergstraesser, E., Dworzak, M., Van Den Heuvel-Eibrink, M. M., De Moerloose, B., Ogawa, S., ... Wlodarski, M. W. (2012). Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML. Blood, 119(11). https://doi.org/10.1182/blood-2011-12-395087