title: Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations.
abstract: OBJECTIVE
  Acquired trisomy 21 is one of the most common numerical abnormalities in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and MDS/MPN; however, little is known about its pathogenic impact, accompanying submicroscopic changes, and its relation to other clinical features. Furthermore, previous studies addressing this issue have mainly focused on cases in which +21 was part of a complex karyotype.
  
  
  METHODS
  We ascertained the incidence of +21, both as a sole change (T21s) and irrespective of additional changes (T21all), in relation to disease type, morphologic subgroup, gender, and age in all published AML, MDS, MPN, and MDS/MPN cases. Furthermore, single nucleotide polymorphism (SNP) array analysis was performed on 11 myeloid malignancies with T21s, followed by mutation analysis of the FGFR1, FLT3, GATA1, JAK2, KIT, NPM1, NRAS, RUNX1, and TET2 genes.
  
  
  RESULTS
  The frequencies of T21s and/or T21all varied significantly among the AML, MDS, MPN, and MDS/MPN cases, among the AML and MPN subtypes, and in relation to the age of the AML, MDS, and MPN patients. In the 11 cases analyzed by SNP array, a total of nine genomic imbalances, comprising seven deletions and two duplications, were identified in six cases; none of the alterations were recurrent. Partial uniparental disomies (UPDs) were found in five cases; two recurrent UPDs were identified, namely UPD4q and UPD7q. Mutations in NPM1, RUNX1, and TET2 were detected in five cases, three of which harbored a pathogenic RUNX1 mutation. The TET2 mutation was found in one of the cases with UPD4q.
  
  
  CONCLUSIONS
  The results show that trisomy 21-positive myeloid malignancies are clinically highly variable and that they display a heterogeneous pattern of copy number alterations and mutations.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. nina.larsson@med.lu.se
authors.forename: Nina
authors.initials: N
authors.lastname: Larsson
authors.forename: Henrik
authors.initials: H
authors.lastname: Lilljebjörn
authors.forename: Carin
authors.initials: C
authors.lastname: Lassen
authors.forename: Bertil
authors.initials: B
authors.lastname: Johansson
authors.forename: Thoas
authors.initials: T
authors.lastname: Fioretos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002891:Chromosomes, Human, Pair 21; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D059785:Karyotype; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D000090243:Nucleophosmin; D020641:Polymorphism, Single Nucleotide; D014314:Trisomy; D055815:Young Adult