title: Chromosomal instability as a prognostic marker in cervical cancer.
abstract: BACKGROUND
  Cervical cancer is the third most common cancer in women globally, and despite treatment, distant metastasis and nodal recurrence will still develop in approximately 30% of patients. The ability to predict which patients are likely to experience distant relapse would allow clinicians to better tailor treatment. Previous studies have investigated the role of chromosomal instability (CIN) in cancer, which can promote tumour initiation and growth; a hallmark of human malignancies. In this study, we sought to examine the published CIN70 gene signature in a cohort of cervical cancer patients treated at the Princess Margaret (PM) Cancer Centre and an independent cohort of The Cancer Genome Atlas (TCGA) cervical cancer patients, to determine if this CIN signature associated with patient outcome.
  
  
  METHODS
  Cervical cancer samples were collected from 79 patients, treated between 2000-2007 at the PM, prior to undergoing curative chemo-radiation. Total RNA was extracted from each patient sample and analyzed using the GeneChip Human Genome U133 Plus 2.0 array (Affymetrix).
  
  
  RESULTS
  High CIN70 scores were significantly related to increased chromosomal alterations in TCGA cervical cancer patients, including a higher percentage of genome altered and a higher number of copy number alterations. In addition, this same CIN70 signature was shown to be predictive of para-aortic nodal relapse in the PM Cancer Centre cohort.
  
  
  CONCLUSIONS
  These findings demonstrate that chromosomal instability plays an important role in cervical cancer, and is significantly associated with patient outcome. For the first time, this CIN70 gene signature provided prognostic value for patients with cervical cancer.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. christine.how@gmail.com.
authors.forename: Christine
authors.initials: C
authors.lastname: How
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. jeffpbruce@gmail.com.
authors.forename: Jeff
authors.initials: J
authors.lastname: Bruce
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. joso42@gmail.com.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. joso42@gmail.com.
authors.forename: Jonathan
authors.initials: J
authors.lastname: So
authors.affiliation: Division of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. pintilie@uhnresearch.ca.
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. bhaibeka@uhnresearch.ca.|Medical Biophysics Department, University of Toronto, Toronto, ON, Canada. bhaibeka@uhnresearch.ca.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. angela.hui@stanford.edu.
authors.forename: Angela
authors.initials: A
authors.lastname: Hui
authors.affiliation: Department of Pathology, University Health Network, Toronto, ON, Canada. blaise.clarke@uhn.on.ca.
authors.forename: Blaise A
authors.initials: BA
authors.lastname: Clarke
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. David.Hedley@uhn.ca.|Division of Medical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada. David.Hedley@uhn.ca.
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. hill@uhnres.utoronto.ca.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Mike.Milosevic@rmp.uhn.on.ca.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. Mike.Milosevic@rmp.uhn.on.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Milosevic
authors.affiliation: Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Anthony.Fyles@rmp.uhn.on.ca.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. Anthony.Fyles@rmp.uhn.on.ca.
authors.forename: Anthony
authors.initials: A
authors.lastname: Fyles
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Fei-Fei.Liu@rmp.uhn.on.ca.|Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. Fei-Fei.Liu@rmp.uhn.on.ca.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. Fei-Fei.Liu@rmp.uhn.on.ca.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D043171:Chromosomal Instability; D005260:Female; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor