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BMC Cancer
Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

Authors: Esther H Lips, Ronald van Eijk, Eelco JR de Graaf, Jan Oosting, Noel FCC de Miranda, Tom Karsten, Cornelis J van de Velde, Paul HC Eilers, Rob AEM Tollenaar, Tom van Wezel, Hans Morreau

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.

Methods

We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.

Results

Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF). The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss.

Conclusion

On basis of integrative analysis this study identified one well known CRC gene (SMAD2) and several other genes (EFNA1, BOP1, TGIF2 and STMN3) that possibly could be used for rectal cancer characterization.
Appendix
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Metadata
Title
Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis
Authors
Esther H Lips
Ronald van Eijk
Eelco JR de Graaf
Jan Oosting
Noel FCC de Miranda
Tom Karsten
Cornelis J van de Velde
Paul HC Eilers
Rob AEM Tollenaar
Tom van Wezel
Hans Morreau
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-314

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