title: Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia.
abstract: BACKGROUND
  The highest rates of cervical cancer are found in developing countries. Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN). CIN lesions described as mild dysplasia (CIN I) are likely to spontaneously regress while CIN III lesions (severe dysplasia) are likely to progress if untreated. Thoughtful consideration of gene expression changes paralleling the progressive pre invasive neoplastic development will yield insight into the key casual events involved in cervical cancer development.
  
  
  RESULTS
  In this study, we have identified gene expression changes across 16 cervical cases (CIN I, CIN II, CIN III and normal cervical epithelium) using the unbiased long serial analysis of gene expression (L-SAGE) method. The 16 L-SAGE libraries were sequenced to the level of 2,481,387 tags, creating the largest SAGE data collection for cervical tissue worldwide. We have identified 222 genes differentially expressed between normal cervical tissue and CIN III. Many of these genes influence biological functions characteristic of cancer, such as cell death, cell growth/proliferation and cellular movement. Evaluation of these genes through network interactions identified multiple candidates that influence regulation of cellular transcription through chromatin remodelling (SMARCC1, NCOR1, MRFAP1 and MORF4L2). Further, these expression events are focused at the critical junction in disease development of moderate dysplasia (CIN II) indicating a role for chromatin remodelling as part of cervical cancer development.
  
  
  CONCLUSIONS
  We have created a valuable publically available resource for the study of gene expression in precancerous cervical lesions. Our results indicate deregulation of the chromatin remodelling complex components and its influencing factors occur in the development of CIN lesions. The increase in SWI/SNF stabilizing molecule SMARCC1 and other novel genes has not been previously illustrated as events in the early stages of dysplasia development and thus not only provides novel candidate markers for screening but a biological function for targeting treatment.
authors.affiliation: Cancer Genetics & Developmental Biology, British Columbia Cancer Research Centre, Vancouver, BC, Canada. ashadeo@bccrc.ca.
authors.forename: Ashleen
authors.initials: A
authors.lastname: Shadeo
authors.forename: Raj
authors.initials: R
authors.lastname: Chari
authors.forename: Kim M
authors.initials: KM
authors.lastname: Lonergan
authors.forename: Andrea
authors.initials: A
authors.lastname: Pusic
authors.forename: Dianne
authors.initials: D
authors.lastname: Miller
authors.forename: Tom
authors.initials: T
authors.lastname: Ehlen
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Niekerk
authors.forename: Jasenka
authors.initials: J
authors.lastname: Matisic
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richards-Kortum
authors.forename: Michele
authors.initials: M
authors.lastname: Follen
authors.forename: Martial
authors.initials: M
authors.lastname: Guillaud
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.forename: Calum
authors.initials: C
authors.lastname: MacAulay
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D015723:Gene Library; D023281:Genomics; D006801:Humans; D016133:Polymerase Chain Reaction; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm