Advanced

mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis

Trager, Catarina; Vernby, Asa; Kullman, Anita; Øra, Ingrid LU ; Kogner, Per and Kagedal, Bertil (2008) In International Journal of Cancer 123(12). p.2849-2855
Abstract
Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of... (More)
Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of children with localized neuroblastoma with increased results in PB did not differ between the three transcripts. In these children, all without morphologically detectable neuroblastoma in BM, the number of patients with elevated GD2S in BM at diagnosis was significantly higher than for the other transcripts (10/16 elevated, P = 0.012). GD2S was elevated in PB from 10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p < 0.001). In BM from these children GD2S was significantly elevated. We conclude that high expression of TH and DDC both in I'll and BM corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome. Children with high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma detection in PB and BM. (C) 2008 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
mRNA, dopa decarboxylase, neuroblastoma, qRT-PCR tyrosine hydroxylase mRNA, GD2 Synthase mRNA, high-risk neuroblastoma
in
International Journal of Cancer
volume
123
issue
12
pages
2849 - 2855
publisher
John Wiley & Sons
external identifiers
  • wos:000261112900016
  • scopus:57349198011
ISSN
0020-7136
DOI
10.1002/ijc.23846
language
English
LU publication?
yes
id
f10f4382-988f-4205-8c3e-586526ede20b (old id 1308682)
date added to LUP
2009-03-19 09:32:39
date last changed
2017-04-02 03:38:16
@article{f10f4382-988f-4205-8c3e-586526ede20b,
  abstract     = {Several transcripts have been claimed to be clinically valuable for detecting minimal disease in neuroblastoma, but they have not been prospectively compared in a standardized manner. Tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and GD2 synthase (GD2S) mRNAs were analyzed in 554 blood (PB) and bone marrow (BM) samples from 58 children with neuroblastoma. Samples from 44 children with other diseases served as controls. High transcript concentrations of TH, GD2S or DDC in PB or BM at diagnosis were associated with poor prognosis. TH in BM above median indicated worse outcome for a homogenous cohort with high-risk neuroblastoma (survival probability 91% for TH below median versus 33% for TH above median, p = 0.009). The number of children with localized neuroblastoma with increased results in PB did not differ between the three transcripts. In these children, all without morphologically detectable neuroblastoma in BM, the number of patients with elevated GD2S in BM at diagnosis was significantly higher than for the other transcripts (10/16 elevated, P = 0.012). GD2S was elevated in PB from 10/28 controls without neuroblastoma compared to 1/28 for TH and DDC (p &lt; 0.001). In BM from these children GD2S was significantly elevated. We conclude that high expression of TH and DDC both in I'll and BM corresponds to metastatic neuroblastoma at diagnosis, residual disease, and poor outcome. Children with high-risk neuroblastoma and low levels of TH in BM at diagnosis may be cured by current therapy. GD2S is less specific than TH and DDC mRNA for neuroblastoma detection in PB and BM. (C) 2008 Wiley-Liss, Inc.},
  author       = {Trager, Catarina and Vernby, Asa and Kullman, Anita and Øra, Ingrid and Kogner, Per and Kagedal, Bertil},
  issn         = {0020-7136},
  keyword      = {mRNA,dopa decarboxylase,neuroblastoma,qRT-PCR tyrosine hydroxylase mRNA,GD2 Synthase mRNA,high-risk neuroblastoma},
  language     = {eng},
  number       = {12},
  pages        = {2849--2855},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {mRNAs of tyrosine hydroxylase and dopa decarboxylase but not of GD2 synthase are specific for neuroblastoma minimal disease and predicts outcome for children with high-risk disease when measured at diagnosis},
  url          = {http://dx.doi.org/10.1002/ijc.23846},
  volume       = {123},
  year         = {2008},
}