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Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia

Paulsson, Kajsa LU ; Biloglav, Andrea LU ; Strömbeck, Bodil LU ; Nilsson, Fredrik; Heldrup, Jesper LU ; Behrendtz, Mikael; Forestier, Erik; Andersson, Anna LU ; Fioretos, Thoas LU and Johansson, Bertil LU (2008) In Genes, Chromosomes and Cancer 47(1). p.26-33
Abstract
Although it has been suggested that mutations of the FLT3, NRAS, KRAS, and PTPN11 genes are particularly frequent in high hyperdiploid (>50 chromosomes) pediatric acute lymphoblastic leukemias (ALLs), this has as yet not been confirmed in a large patient cohort. Furthermore, it is unknown whether mutations of these genes coexist in hyperdiploid cases. We performed mutation analyses of FLT3, NRAS, KRAS, and PTPN11 in a consecutive series of 78 high hyperdiploid ALLs. Twenty-six (33%) of the cases harbored a mutation, comprising six activating point mutations and one internal tandem duplication of FLT3 (7/78 cases; 9.0%), eight codon 12, 13, or 61 NRAS mutations (8/78 cases; 10%), five codon 12 or 13 KRAS mutations (5/78 cases, 6.4%), and... (More)
Although it has been suggested that mutations of the FLT3, NRAS, KRAS, and PTPN11 genes are particularly frequent in high hyperdiploid (>50 chromosomes) pediatric acute lymphoblastic leukemias (ALLs), this has as yet not been confirmed in a large patient cohort. Furthermore, it is unknown whether mutations of these genes coexist in hyperdiploid cases. We performed mutation analyses of FLT3, NRAS, KRAS, and PTPN11 in a consecutive series of 78 high hyperdiploid ALLs. Twenty-six (33%) of the cases harbored a mutation, comprising six activating point mutations and one internal tandem duplication of FLT3 (7/78 cases; 9.0%), eight codon 12, 13, or 61 NRAS mutations (8/78 cases; 10%), five codon 12 or 13 KRAS mutations (5/78 cases, 6.4%), and seven exon 3 or 13 PTPN11 mutations (7/78 cases; 9.0%). No association was seen between the presence of a mutation in FLT3, NRAS, KRAS, or PTPN11 and gender, age, white blood cell count, or relapse, suggesting that they do not confer a negative prognostic impact. Only one case harbored mutations in two different genes, suggesting that mutations of these four genes are generally mutually exclusive. In total, one third of the cases harbored a FLT3, NRAS, KRAS, or PTPN11 mutation, identifying the RTK-RAS signaling pathway as a potential target for novel therapies of high hyperdiploid pediatric ALLs. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
47
issue
1
pages
26 - 33
publisher
John Wiley & Sons
external identifiers
  • pmid:17910045
  • wos:000251365800004
  • scopus:36549062445
ISSN
1045-2257
DOI
10.1002/gcc.20502
language
English
LU publication?
yes
id
52c8ae14-0be5-4ac8-b37b-9d6fa2cfab6a (old id 1137797)
date added to LUP
2009-07-10 11:21:54
date last changed
2017-08-27 04:10:56
@article{52c8ae14-0be5-4ac8-b37b-9d6fa2cfab6a,
  abstract     = {Although it has been suggested that mutations of the FLT3, NRAS, KRAS, and PTPN11 genes are particularly frequent in high hyperdiploid (>50 chromosomes) pediatric acute lymphoblastic leukemias (ALLs), this has as yet not been confirmed in a large patient cohort. Furthermore, it is unknown whether mutations of these genes coexist in hyperdiploid cases. We performed mutation analyses of FLT3, NRAS, KRAS, and PTPN11 in a consecutive series of 78 high hyperdiploid ALLs. Twenty-six (33%) of the cases harbored a mutation, comprising six activating point mutations and one internal tandem duplication of FLT3 (7/78 cases; 9.0%), eight codon 12, 13, or 61 NRAS mutations (8/78 cases; 10%), five codon 12 or 13 KRAS mutations (5/78 cases, 6.4%), and seven exon 3 or 13 PTPN11 mutations (7/78 cases; 9.0%). No association was seen between the presence of a mutation in FLT3, NRAS, KRAS, or PTPN11 and gender, age, white blood cell count, or relapse, suggesting that they do not confer a negative prognostic impact. Only one case harbored mutations in two different genes, suggesting that mutations of these four genes are generally mutually exclusive. In total, one third of the cases harbored a FLT3, NRAS, KRAS, or PTPN11 mutation, identifying the RTK-RAS signaling pathway as a potential target for novel therapies of high hyperdiploid pediatric ALLs.},
  author       = {Paulsson, Kajsa and Biloglav, Andrea and Strömbeck, Bodil and Nilsson, Fredrik and Heldrup, Jesper and Behrendtz, Mikael and Forestier, Erik and Andersson, Anna and Fioretos, Thoas and Johansson, Bertil},
  issn         = {1045-2257},
  language     = {eng},
  number       = {1},
  pages        = {26--33},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia},
  url          = {http://dx.doi.org/10.1002/gcc.20502},
  volume       = {47},
  year         = {2008},
}