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ERBB3 is a marker o...
ERBB3 is a marker of a ganglioneuroblastoma/ganglioneuroma-like expression profile in neuroblastic tumours
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- Wilzén, Annica (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics
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- Krona, Cecilia (author)
- Karolinska universitetssjukhuset,Karolinska University Hospital
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- Sveinbjornsson, Baldur (author)
- Karolinska Institutet
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- Kristiansson, Erik, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics
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- Dalevi, Daniel, 1974 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Øra, Ingrid (author)
- Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine
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De Preter, Katleen (author)
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Stallings, Raymond L. (author)
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- Maris, John (author)
- University of Pennsylvania
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- Versteeg, Rogier (author)
- Universiteit Van Amsterdam,University of Amsterdam
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- Nilsson, Staffan, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics
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- Kogner, Per (author)
- Karolinska Institutet
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- Abel, Frida, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics
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(creator_code:org_t)
- 2013-07-08
- 2013
- English.
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In: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 12
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Abstract
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- Background: Neuroblastoma (NB) tumours are commonly divided into three cytogenetic subgroups. However, by unsupervised principal components analysis of gene expression profiles we recently identified four distinct subgroups, r1-r4. In the current study we characterized these different subgroups in more detail, with a specific focus on the fourth divergent tumour subgroup (r4). Methods: Expression microarray data from four international studies corresponding to 148 neuroblastic tumour cases were subject to division into four expression subgroups using a previously described 6-gene signature. Differentially expressed genes between groups were identified using Significance Analysis of Microarray (SAM). Next, gene expression network modelling was performed to map signalling pathways and cellular processes representing each subgroup. Findings were validated at the protein level by immunohistochemistry and immunoblot analyses. Results: We identified several significantly up-regulated genes in the r4 subgroup of which the tyrosine kinase receptor ERBB3 was most prominent (fold change: 132-240). By gene set enrichment analysis (GSEA) the constructed gene network of ERBB3 (n = 38 network partners) was significantly enriched in the r4 subgroup in all four independent data sets. ERBB3 was also positively correlated to the ErbB family members EGFR and ERBB2 in all data sets, and a concurrent overexpression was seen in the r4 subgroup. Further studies of histopathology categories using a fifth data set of 110 neuroblastic tumours, showed a striking similarity between the expression profile of r4 to ganglioneuroblastoma (GNB) and ganglioneuroma (GN) tumours. In contrast, the NB histopathological subtype was dominated by mitotic regulating genes, characterizing unfavourable NB subgroups in particular. The high ErbB3 expression in GN tumour types was verified at the protein level, and showed mainly expression in the mature ganglion cells. Conclusions: Conclusively, this study demonstrates the importance of performing unsupervised clustering and subtype discovery of data sets prior to analyses to avoid a mixture of tumour subtypes, which may otherwise give distorted results and lead to incorrect conclusions. The current study identifies ERBB3 as a clear-cut marker of a GNB/GN-like expression profile, and we suggest a 7-gene expression signature (including ERBB3) as a complement to histopathology analysis of neuroblastic tumours. Further studies of ErbB3 and other ErbB family members and their role in neuroblastic differentiation and pathogenesis are warranted.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- Microarray
- Expression
- Cancer
- Systems biology
- Oncology
- Network
- Reverse engineering
- Unsupervised
- Clustering
- Cell cycle
- Spindle
- assembly
- Her-3
- HER3
- ERBB3
- Her-2
- HER2
- ERBB2
- EGFR
- ERBB1
- BIRC5
- Survivin
- MYCN
- N-myc
- ALK
- PHOX2B
- NTRK1
- CCND1
- genetics expression analysis systems biology tumor neuroblastoma
- genetics expression analysis systems biology tumor neuroblastoma
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Wilzén, Annica
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Krona, Cecilia
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Sveinbjornsson, ...
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Kristiansson, Er ...
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Dalevi, Daniel, ...
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Øra, Ingrid
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show more...
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De Preter, Katle ...
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Stallings, Raymo ...
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Maris, John
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Versteeg, Rogier
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Nilsson, Staffan ...
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Kogner, Per
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Abel, Frida, 197 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Molecular Cancer
- By the university
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Lund University
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Chalmers University of Technology
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University of Gothenburg
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Karolinska Institutet