Dataset Information

Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia.

ABSTRACT: 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.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.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.

SUBMITTER: Shadeo A

PROVIDER: S-EPMC2277413 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia.

Shadeo Ashleen A Chari Raj R Lonergan Kim M KM Pusic Andrea A Miller Dianne D Ehlen Tom T Van Niekerk Dirk D Matisic Jasenka J Richards-Kortum Rebecca R Follen Michele M Guillaud Martial M Lam Wan L WL MacAulay Calum C

BMC genomics 20080204

<h4>Background</h4>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 pa ...[more]

PMID: 18248679

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Project description:Analysis of various of up-regulated and down-regulated genes in Normal Cervical mucosa, Cervical intraepithelial neoplasia and Cervical squamous cell carcinoma. The report provides a data analysis methodology for identification of co-expressed gene patterns, as emerging clusters, in global transcriptome of cervical mucosal pre-malignant and malignant conditions in comparison to their normal counterparts. Microarray based study of global gene expression is often used to extract molecular signatures underlying cancer progression. Such endeavors endorse self organizing map, a type of artificial neural network to analyze high dimensional pre-processed transcriptome data to segregate hotspot genes in component plane for disease subtypes. This report provides a data analysis methodology for identification of coexpressed gene patterns, as emerging clusters, in global transcriptome of oral and cervical mucosal premalignant and malignant conditions in comparison to their normal counterparts. Four exclusive cluster patterns, each involving 100 − 300 genes, were identified from component planes for oral study groups. Gene expression associated with each pattern belonged to 32 biological processes. Analysis on cervical biopsies, where cancer was compared to cervical interepithelial neoplasia and normal counterpart, it revealed three non-overlapping patterns for each condition. In cervical interepithelial neoplasia an intermediate pattern with nine different dominant functional processes was identified, whereas, in cervical squamous cell carcinoma pattern showed dominance for seven different functions. This analysis demonstrated utility of self organizing map to capture dominant enriched patterns as visual plots and revealed six common biological processes like transcription and RNA processing, cytoskeleton reorganization, angiogenesis, immunity, neuron signalling, and connective tissue remodelling in the pathogenesis of oral and cervical cancers. In fact it could provide an intuitive understanding of molecular course in carcinogenesis and may contribute for combinatorial biomarker discovery.

Dataset Information

Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia.

Publications

Up regulation in gene expression of chromatin remodelling factors in cervical intraepithelial neoplasia.

Similar Datasets

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