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Whole-exome sequencing of pediatric acute lymphoblastic leukemia.

Lilljebjörn, Henrik LU ; Rissler, Marianne LU ; Lassen, Carin LU ; Heldrup, Jesper LU ; Behrendtz, M; Mitelman, Felix LU ; Johansson, Bertil LU and Fioretos, Thoas LU (2012) In Leukemia 26. p.1602-1607
Abstract
Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering... (More)
Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.Leukemia advance online publication, 18 November 2011; doi:10.1038/leu.2011.333. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
26
pages
1602 - 1607
publisher
Nature Publishing Group
external identifiers
  • wos:000306307600020
  • pmid:22094584
  • scopus:84863782843
ISSN
1476-5551
DOI
10.1038/leu.2011.333
language
English
LU publication?
yes
id
e3f3ea69-91a7-4a3f-877c-95bd1ec54820 (old id 2220651)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22094584?dopt=Abstract
date added to LUP
2011-12-02 22:15:37
date last changed
2017-07-30 04:02:58
@article{e3f3ea69-91a7-4a3f-877c-95bd1ec54820,
  abstract     = {Acute lymphoblastic leukemia (ALL), the most common malignant disorder in childhood, is typically associated with numerical chromosomal aberrations, fusion genes or small focal deletions, thought to represent important pathogenetic events in the development of the leukemia. Mutations, such as single nucleotide changes, have also been reported in childhood ALL, but these have only been studied by sequencing a small number of candidate genes. Herein, we report the first unbiased sequencing of the whole exome of two cases of pediatric ALL carrying the ETV6/RUNX1 (TEL/AML1) fusion gene (the most common genetic subtype) and corresponding normal samples. A total of 14 somatic mutations were identified, including four and seven protein-altering nucleotide substitutions in each ALL. Twelve mutations (86%) occurred in genes previously described to be mutated in other types of cancer, but none was found to be recurrent in an extended series of 29 ETV6/RUNX1-positive ALLs. The number of single nucleotide mutations was similar to the number of copy number alterations as detected by single nucleotide polymorphism arrays. Although the true pathogenetic significance of the mutations must await future functional evaluations, this study provides a first estimate of the mutational burden at the genetic level of t(12;21)-positive childhood ALL.Leukemia advance online publication, 18 November 2011; doi:10.1038/leu.2011.333.},
  author       = {Lilljebjörn, Henrik and Rissler, Marianne and Lassen, Carin and Heldrup, Jesper and Behrendtz, M and Mitelman, Felix and Johansson, Bertil and Fioretos, Thoas},
  issn         = {1476-5551},
  language     = {eng},
  pages        = {1602--1607},
  publisher    = {Nature Publishing Group},
  series       = {Leukemia},
  title        = {Whole-exome sequencing of pediatric acute lymphoblastic leukemia.},
  url          = {http://dx.doi.org/10.1038/leu.2011.333},
  volume       = {26},
  year         = {2012},
}