title: Gene expression profiling of human dermal fibroblasts exposed to bleomycin sulphate does not differentiate between radiation sensitive and control patients.
abstract: BACKGROUND
  Gene expression profiling of the transcriptional response of human dermal fibroblasts to in vitro radiation has shown promise as a predictive test of radiosensitivity. This study tested if treatment with the radiomimetic drug bleomycin sulphate could be used to differentiate radiation sensitive patients and controls in patients who had previously received radiotherapy for early breast cancer.
  
  
  RESULTS
  Eight patients who developed marked late radiation change assessed by photographic breast appearance and 8 matched patients without any change were selected from women entered in a prospective randomised trial of breast radiotherapy fractionation. Gene expression profiling of primary skin fibroblasts exposed in vitro to bleomycin sulphate and mock treated fibroblast controls was performed. 973 genes were up-regulated and 923 down-regulated in bleomycin sulphate treated compared to mock treated control fibroblasts. Gene ontology analysis revealed enriched groups were cellular localisation, apoptosis, cell cycle and DNA damage response for the deregulated genes. No transcriptional differences were identified between fibroblasts from radiation sensitive cases and control patients; subgroup analysis using cases exhibiting severe radiation sensitivity or with high risk alleles present in TGF β1 also showed no difference.
  
  
  CONCLUSIONS
  The transcriptional response of human dermal fibroblasts to bleomycin sulphate has been characterised. No differences between clinically radiation sensitive and control patients were detected using this approach.
authors.affiliation: Department of Radiotherapy, The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Westbury
authors.forename: Kristine Kleivi
authors.initials: KK
authors.lastname: Sahlberg
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Borresen-Dale
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
authors.forename: John R
authors.initials: JR
authors.lastname: Yarnold
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000494:pharmacology*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D011836:Radiation Tolerance; D012867:Skin / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D012313:RNA