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Genomic characterization of ETV6/RUNX1-positive acute lymphoblastic leukemia

Lilljebjörn, Henrik LU (2011) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2011:18.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Schmiegelow, Kjeld, Department of Paediatrics, The University Hospital Rigshospitalet, Copenhagen, Denmark
organization
publishing date
type
Thesis
publication status
published
subject
keywords
SNP array, array CGH, ETV6/RUNX1-positive ALL, childhood ALL, exome sequencing
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2011:18
pages
61 pages
publisher
Lund University
defense location
Föreläsningssal F3, Universitetssjukhuset i Lund
defense date
2011-03-11 09:00
ISSN
1652-8220
ISBN
978-91-86671-67-9
language
English
LU publication?
yes
id
7961898b-a218-45c4-8ac7-655a01f54588 (old id 1787221)
date added to LUP
2011-02-15 14:59:52
date last changed
2016-09-19 08:44:46
@phdthesis{7961898b-a218-45c4-8ac7-655a01f54588,
  abstract     = {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.},
  author       = {Lilljebjörn, Henrik},
  isbn         = {978-91-86671-67-9},
  issn         = {1652-8220},
  keyword      = {SNP array,array CGH,ETV6/RUNX1-positive ALL,childhood ALL,exome sequencing},
  language     = {eng},
  pages        = {61},
  publisher    = {Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Genomic characterization of ETV6/RUNX1-positive acute lymphoblastic leukemia},
  volume       = {2011:18},
  year         = {2011},
}