Genomic characterization of ETV6/RUNX1-positive acute lymphoblastic leukemia

Research output: ThesisDoctoral Thesis (compilation)

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The t(12;21) translocation generates the ETV6/RUNX1 fusion gene, present in 25% of childhood acute lymphoblastic leukemia. This fusion gene is important for leukemia development but is not sufficient for leukemia to arise. Hence, the additional genetic changes present in leukemic ETV6/RUNX1-positive cells give important clues regarding the history of the leukemia. The aim of this thesis has been to characterize thoroughly the genetic changes present in ETV6/RUNX1-positive ALL. In Article I, seventeen ETV6/RUNX1-positive ALLs were characterized using array CGH. This revealed that gain of Xq material, present in six cases, was the most common copy number aberration (CNA). A large number of genes was present in the commonly gained region but the high and specific expression of SPANXB identified this gene as a likely target of the gain. In Article II, 24 ALLs were analyzed using 500K single nucleotide polymorphism arrays. The data from these ALLs were combined with previously published external SNP array data from 140 ETV6/RUNX1-positive ALLs. A high number of recurrent CNAs could be identified in this dataset. The recurrent CNAs were further analyzed using hierarchical clustering, connected pair analysis, and oncogenetic tree models. These analyzes revealed that the majority of cases had acquired a unique set of recurrent CNAs, indicating that the process of acquiring CNAs is unique for each ALL. In Article III, exome sequencing was used to sequence all protein coding genes in two ETV6/RUNX1-positive ALLs. Seven somatic single nucleotide mutations were present in each ALL, six of these were in genes previously implicated in cancer.
Original languageEnglish
Awarding Institution
  • Division of Clinical Genetics
  • Fioretos, Thoas, Supervisor
  • Hagström-Andersson, Anna, Supervisor
  • Johansson, Bertil, Supervisor
Award date2011 Mar 11
ISBN (Print)978-91-86671-67-9
Publication statusPublished - 2011

Bibliographical note

Defence details

Date: 2011-03-11
Time: 09:00
Place: Föreläsningssal F3, Universitetssjukhuset i Lund

External reviewer(s)

Name: Schmiegelow, Kjeld
Title: [unknown]
Affiliation: Department of Paediatrics, The University Hospital Rigshospitalet, Copenhagen, Denmark


Subject classification (UKÄ)

  • Medical Genetics

Free keywords

  • SNP array
  • array CGH
  • ETV6/RUNX1-positive ALL
  • childhood ALL
  • exome sequencing


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