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The Phox2 pathway is differentially expressed in neuroblastoma tumors, but no mutations were found in the candidate tumor suppressor gene PHOX2A.

Journal article
Authors Annica Wilzén
Staffan Nilsson
Rose-Marie Sjöberg
Per Kogner
Tommy Martinsson
Frida Abel
Published in International journal of oncology
Volume 34
Issue 3
Pages 697-705
ISSN 1019-6439
Publication year 2009
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Department of Mathematical Sciences, Mathematical Statistics
Pages 697-705
Language en
Links dx.doi.org/10.3892/ijo_00000196
Subject categories Medical and Health Sciences

Abstract

Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common solid tumor in childhood. By microarray expression analysis (Affymetrix HU133A) important players in the noradrenalin biosynthesis pathway (DBH, DDC, GATA2, GATA3, PHOX2A, PHOX2B, SLC6A2 SLC18A1 and TH) were found to be among the top ranked genes in showing lower expression in unfavorable NB tumor types as compared to favorable ones. By quantitative PCR with TaqMan, this result was significantly verified for all transcripts (p<0.05, one-tailed) in a new set of 11 primary NB tumors (5 favorable vs. 6 unfavorable). PHOX2A, a downstream target of Phox2b, was found to be the sixth ranked gene from the microarray gene list. Since the PHOX2A gene is localized in a tumor suppressor candidate region at 11q, we screened this gene for mutations by DNA sequencing in 47 tumors of different stages. However, no critical changes were found that could support its role in tumor development or progression. Overall, the findings in this study either suggest that expression of this pathway could be a predictive differentiation marker of NB tumors, or our results could also imply that the noradrenalin biosynthesis pathway is involved in tumor pathogenesis.

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