title: BARD1 expression predicts outcome in colon cancer.
abstract: OBJECTIVE
  BARD1 is a BRCA1-binding partner with tumor suppressive properties. Aberrant splice variants of BARD1 have been detected in various cancers, and it has been postulated that the presence of some splice variants is cancer specific. This is the first study assessing BARD1 expression patterns and correlation with clinical outcome in colon cancer.
  
  
  METHODS
  We analyzed colon cancer samples for the occurrence of BARD1 splice variants, characterized novel BARD1 splice variants, and quantified the mRNA expression levels of these isoforms in primary colon cancers and their corresponding normal tissue. We tested the correlation of full-length BARD1 protein expression and clinical outcome in primary colon cancer samples.
  
  
  RESULTS
  In addition to the full-length BARD1 mRNA, we now find 19 distinct BARD1 splice variants in colon cancer. Contrary to previous assumptions, these splice variants also occur in the adjacent normal colon tissue. Although BARD1 splice variants account for a considerable amount of BARD1 mRNA in both cancer and normal colon samples, distinct variants show a cancer-specific regulation pattern. Consistent with its role as tumor suppressor, we further find that the expression of the full-length BARD1 protein predicts outcome in colon cancer and that loss of full-length BARD1 protein is associated with a poor prognosis (P = 0.0002).
  
  
  CONCLUSIONS
  Taken together, this is the first report to suggest that BARD1 regulation is an important pathway in colon cancer and that the BARD1 full-length protein may be a useful marker to improve risk stratification in colon cancer patients.
authors.affiliation: Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sporn
authors.forename: Torsten
authors.initials: T
authors.lastname: Hothorn
authors.forename: Barbara
authors.initials: B
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015331:Cohort Studies; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D005472:Fluorouracil