The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations

Genes Chromosomes Cancer. 2016 Oct;55(10):777-85. doi: 10.1002/gcc.22377. Epub 2016 Jul 4.

Abstract

Deletions in the long arm of chromosome 5 (del(5q)) are recurrent abnormalities in myeloid malignancies. We analyzed del(5q) and accompanying molecular mutations in MDS, MPN and MDS/MPN cases. A high del(5q) frequency was revealed in MDS (1869/11398 cases; 16%), followed by MDS/MPN (37/1107; 3%) and MPN (97/6373; 2%). To investigate potential associations of the del(5q) size with the respective phenotypes, we applied array CGH analyses in selected cohorts of 61 MDS, 22 MDS/MPN and 23 MPN cases. The size varied between 16 and 119 Mb with no differences between the entities. However, MPN and MDS/MPN cases with del(5q) sole showed a significantly smaller del(5q) than cases with additional aberrations. Sequence analysis of 27 genes revealed ≥1 mutation in 91% of patients. The highest mutation frequencies in the total cohort were observed for TP53 (31%), JAK2 (23%) and DNMT3A (18%). The molecular mutation patterns in the del(5q) cohorts were different between the entities but resembled known patterns of cohorts not selected for del(5q). Further, TP53 mutations were significantly more frequent in cases with a larger deletion size (P = 0.003). The results suggest a correlation of large del(5q) with TP53 mutations and with additional chromosomal aberrations possibly contributing to more severe courses of these cases. © 2016 Wiley Periodicals, Inc.

MeSH terms

  • Chromosome Deletion
  • Chromosomes, Human, Pair 5 / genetics*
  • Comparative Genomic Hybridization
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA Methyltransferase 3A
  • DNA Mutational Analysis
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Janus Kinase 2 / genetics
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Mutation / genetics
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / pathology
  • Neoplasm Proteins / genetics
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • DNMT3A protein, human
  • Neoplasm Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • JAK2 protein, human
  • Janus Kinase 2