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
- 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
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Genes, Chromosomes and Cancer
- volume
- 47
- issue
- 1
- pages
- 26 - 33
- publisher
- John Wiley & Sons Inc.
- 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
- 2016-04-01 12:14:24
- date last changed
- 2022-03-28 22:13:15
@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 Inc.}},
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}},
doi = {{10.1002/gcc.20502}},
volume = {{47}},
year = {{2008}},
}