Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis Export

@article{citeulike:3464645, 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.}, author = {Lips, Esther and van Eijk, Ronald and de Graaf, Eelco and Oosting, Jan and de Miranda, Noel and Karsten, Tom and van de Velde, Cornelis and Eilers, Paul and Tollenaar, Rob and van Wezel, Tom and Morreau, Hans}, citeulike-article-id = {3464645}, citeulike-linkout-0 = {http://dx.doi.org/10.1186/1471-2407-8-314}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18959792}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18959792}, doi = {10.1186/1471-2407-8-314}, issn = {1471-2407}, journal = {BMC Cancer}, keywords = {aberration, cancer, chromosomal, data, genomic, microarray, rectal}, number = {1}, pages = {314+}, posted-at = {2008-11-20 23:00:00}, priority = {2}, title = {Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis}, url = {http://dx.doi.org/10.1186/1471-2407-8-314}, volume = {8}, year = {2008} }

TY - JOUR ID - citeulike:3464645 L3 - citeulike-article-id:3464645 N2 - 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. IS - 1 JF - BMC Cancer SN - 1471-2407 TI - Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis VL - 8 SP - 314 KW - aberration KW - cancer KW - chromosomal KW - data KW - genomic KW - microarray KW - rectal AU - Lips, Esther AU - van Eijk, Ronald AU - de Graaf, Eelco AU - Oosting, Jan AU - de Miranda, Noel AU - Karsten, Tom AU - van de Velde, Cornelis AU - Eilers, Paul AU - Tollenaar, Rob AU - van Wezel, Tom AU - Morreau, Hans PY - 2008/// UR - http://dx.doi.org/10.1186/1471-2407-8-314 ER -