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Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors and associated with clinical outcome

Skotheim, RI; Kallioniemi, A; Bjerkhagen, B; Mertens, Fredrik LU ; Brekke, HR; Monni, O; Mousses, S; Mandahl, N; Saeter, G and Nesland, JM, et al. (2003) In Journal of Clinical Oncology 21(24). p.4586-4591
Abstract
Purpose: To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists. Materials and Methods: Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate... (More)
Purpose: To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists. Materials and Methods: Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate genes were examined and related to clinical end points. Results: Among several deregulated genes found by cDNA microarray analyses, topoisomerase IIalpha (TOP2A) was the most overexpressed gene in MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing tumors were associated with poor cancer-specific survival and presence of metastases. Conclusion: We have identified TOP2A as a target gene in MPNST, using a focused gene expression profiling followed by a DNA copy number evaluation and clinical validation of the encoded protein using a tissue microarray. This study is the first to suggest that TOP2A expression may be a predictive factor for adverse outcome in MPNST. (C) 2003 by American Society of Clinical Oncology. (Less)
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Journal of Clinical Oncology
volume
21
issue
24
pages
4586 - 4591
publisher
American Society of Clinical Oncology
external identifiers
  • wos:000187432300021
  • pmid:14673046
  • scopus:1542438624
ISSN
1527-7755
DOI
10.1200/JCO.2003.07.067
language
English
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yes
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bed61bd1-1ed2-4b77-a05e-86156f8c62df (old id 291364)
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http://jco.ascopubs.org/cgi/content/abstract/21/24/4586
date added to LUP
2007-09-22 10:44:06
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2018-10-03 10:20:02
@article{bed61bd1-1ed2-4b77-a05e-86156f8c62df,
  abstract     = {Purpose: To identify target genes of clinical significance for patients with malignant peripheral-nerve sheath tumor (MPNST), an aggressive cancer for which no consensus therapy exists. Materials and Methods: Biopsies and clinical data from 51 patients with MPNST were included in this study. Based on our previous research implicating chromosome arm 17q amplification in MPNST, we performed gene expression analyses of 14 MPNSTs using chromosome 17-specific cDNA microarrays. Copy numbers of selected gene probes and centromere probes were then determined by interphase fluorescence in situ hybridization in 16 MPNSTs. Finally, we generated a tissue microarray containing 79 samples from 44 MPNSTs, on which in situ protein expressions of candidate genes were examined and related to clinical end points. Results: Among several deregulated genes found by cDNA microarray analyses, topoisomerase IIalpha (TOP2A) was the most overexpressed gene in MPNSTs compared with benign neurofibromas. Excess copies of the TOP2A were also seen at the DNA level in 10 of 16 cases, and high expression of the TOP2A protein was seen in 83% of the tumors on the tissue microarray. The TOP2A-expressing tumors were associated with poor cancer-specific survival and presence of metastases. Conclusion: We have identified TOP2A as a target gene in MPNST, using a focused gene expression profiling followed by a DNA copy number evaluation and clinical validation of the encoded protein using a tissue microarray. This study is the first to suggest that TOP2A expression may be a predictive factor for adverse outcome in MPNST. (C) 2003 by American Society of Clinical Oncology.},
  author       = {Skotheim, RI and Kallioniemi, A and Bjerkhagen, B and Mertens, Fredrik and Brekke, HR and Monni, O and Mousses, S and Mandahl, N and Saeter, G and Nesland, JM and Smeland, S and Kallioniemi, OP and Lothe, RA},
  issn         = {1527-7755},
  language     = {eng},
  number       = {24},
  pages        = {4586--4591},
  publisher    = {American Society of Clinical Oncology},
  series       = {Journal of Clinical Oncology},
  title        = {Topoisomerase-II alpha is upregulated in malignant peripheral nerve sheath tumors and associated with clinical outcome},
  url          = {http://dx.doi.org/10.1200/JCO.2003.07.067},
  volume       = {21},
  year         = {2003},
}