title: Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, the Netherlands. j.morreau@Lumc.nl.
authors.forename: Esther H
authors.initials: EH
authors.lastname: Lips
authors.forename: Ronald
authors.initials: R
authors.lastname: van Eijk
authors.forename: Eelco J R
authors.initials: EJ
authors.lastname: de Graaf
authors.forename: Jan
authors.initials: J
authors.lastname: Oosting
authors.forename: Noel F C C
authors.initials: NF
authors.lastname: de Miranda
authors.forename: Tom
authors.initials: T
authors.lastname: Karsten
authors.forename: Cornelis J
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: Paul H C
authors.initials: PH
authors.lastname: Eilers
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.forename: Tom
authors.initials: T
authors.lastname: van Wezel
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
mesh_terms: D002869:Chromosome Aberrations; D002887:Chromosomes, Human, Pair 18; D002890:Chromosomes, Human, Pair 20; D002898:Chromosomes, Human, Pair 8; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics; D050777:Stathmin / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C514383:BOP1 protein, human; D018398:Homeodomain Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C497782:SMAD2 protein, human; C112285:STMN3 protein, human; D051899:Smad2 Protein; D050777:Stathmin; C414585:TGIF2 protein, human; D042461:Vascular Endothelial Growth Factor A