title: Mutations of the PTPN11 gene in therapy-related MDS and AML with rare balanced chromosome translocations.
abstract: Activating mutations of the PTPN11 gene encoding the SHP2 tyrosine phosphatase is the most common genetic abnormality in juvenile myelomonocytic leukemia and is sporadically observed in myelodysplasia (MDS) and acute myeloid leukemia (AML). An unselected series of 140 patients with therapy-related MDS or AML were investigated for mutations of PTPN11 in Exons 3, 4, 8, and 13. Four cases had mutations of the gene; three of these had deletions or loss of chromosome arm 7q. Two cases had rare balanced translocations to chromosome band 21q22 with rearrangement of the RUNX1 gene and the other two patients had rare balanced translocations to chromosome band 3q26 with rearrangement of the EVI1 gene. The findings support cooperation between so called Class I and Class II mutations in leukemogenesis.
authors.affiliation: Cytogenetic Laboratory, Section of Hematology/Oncology, Department of Clinical Genetics, The Juliane Marie Center, Copenhagen DK 2100 Ø, Denmark.
authors.forename: Debes H
authors.initials: DH
authors.lastname: Christiansen
authors.forename: Frehiwet
authors.initials: F
authors.lastname: Desta
authors.forename: Mette K
authors.initials: MK
authors.lastname: Andersen
authors.forename: Jens
authors.initials: J
authors.lastname: Pedersen-Bjergaard
mesh_terms: D000208:Acute Disease; D000368:Aged; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases