C76
Comprehensive serial analysis of gene expression of the cervical epithelium transcriptome
Ashleen Shadeo, Jennifer Y. Kennett, Raj Chari, Calum MacAulay, Wan L. Lam
BC Cancer Research Centre, Vancouver, BC, Canada
Background
Approximately 500,000 women are diagnosed with cervical cancer worldwide each year and more than half of them will die from this disease. Cervical intraepithelial neoplasia (CIN) is a precursor lesion to cervical cancer and can be further subclassified into three groups: CIN I, CIN II and CIN III (mild, moderate and severe dysplasia, respectively). Most CIN I lesions spontaneously regress to normal cervical epithelia whereas CIN III lesions are much more likely to progress to cervical cancer if left untreated. Therefore, CIN II may represent a critical junction in disease development. A thorough understanding of genetic events in preinvasive lesions will yield insight to the early stages of disease and is required to identify causal events in cervical cancer.
Method
In this study we have analyzed and compared the transcriptome across sixteen cases (CIN I, CIN II, CIN III and normal cervical epithelium) using an unbiased long serial analysis of gene expression (L-SAGE) method. In total, sixteen L-SAGE libraries were sequenced to 2,481,387 tags, establishing the largest SAGE data collection for cervical tissue worldwide.
Results
We identified 108 tags increased in frequency in CIN III and 138 tags decreased and overall observed 246 tags differentially expressed between normal cervical tissue and CIN III using a modified Z-test. Biological functions most influenced by these genes include cell death, cell growth/proliferation and cellular movement. In addition, we have identified twelve unique Human Papillomavirus 16 (HPV 16) tags in the CIN III libraries.
Conclusion
Gene expression changes that parallel the progression stages will help to further our understanding of cervical cancer development and identify novel treatment targets. In evaluation of expression differences between normal and CIN lesions, we identified two gene networks targeted. Several of these genes directly or indirectly involve chromatin remodelling or the SWI/SNF ATPase chromatin remodelling complex. In addition, these disruptions may be targeted to the critical stage of moderate dysplasia (CIN II) and provide candidate markers for screening at this junction.
