KRAS and CREBBP mutations: A relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia

K. Malinowska-Ozdowy, C. Frech, A. Schönegger, C. Eckert, G. Cazzaniga, M. Stanulla, U. Zur Stadt, A. Mecklenbräuker, M. Schuster, D. Kneidinger, A. Von Stackelberg, F. Locatelli, M. Schrappe, M. A. Horstmann, A. Attarbaschi, C. Bock, G. Mann, O. A. Haas, R. Panzer-Grümayer

Research output: Contribution to journalArticlepeer-review

Abstract

High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P

Original languageEnglish
Pages (from-to)1656-1667
Number of pages12
JournalLeukemia
Volume29
Issue number8
DOIs
Publication statusPublished - Aug 7 2015

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Fingerprint Dive into the research topics of 'KRAS and CREBBP mutations: A relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia'. Together they form a unique fingerprint.

Cite this