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

Shadeo A, Chari R, Lonergan KM, Pusic A, Miller D, Ehlen T, Van Niekerk D, Matisic J, Richards-Kortum R, Follen M, Guillaud M, Lam WL, MacAulay C - BMC Genomics (2008)

Bottom Line: Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Genetics & Developmental Biology, British Columbia Cancer Research Centre, Vancouver, BC, Canada. ashadeo@bccrc.ca.

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.

Conclusion: 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.

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Related in: MedlinePlus

An updated box plot from Guillaud et al. showing the correlation between a linear discriminant function score (Texture Score) based entirely on only texture phenotype features measured of the nuclei in formalin fixed quantitatively stained sections of biopsied tissue [39]. The error bars represent the 5th and 95th percentiles; the box represents the central 50th percentile and the solid square the mean of the distribution of the scores for measured sections with the noted histopathological diagnosis. The numbers over the boxes are the number of samples measured for the specific diagnosis.
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Figure 7: An updated box plot from Guillaud et al. showing the correlation between a linear discriminant function score (Texture Score) based entirely on only texture phenotype features measured of the nuclei in formalin fixed quantitatively stained sections of biopsied tissue [39]. The error bars represent the 5th and 95th percentiles; the box represents the central 50th percentile and the solid square the mean of the distribution of the scores for measured sections with the noted histopathological diagnosis. The numbers over the boxes are the number of samples measured for the specific diagnosis.

Mentions: This differential expression in the chromatin remodelling genes could result in changes in the organization of the DNA. If these changes are large enough they could be detectable. Previously, we quantified changes in nuclear texture with increasing grade of CIN [39]. These measured phenotype changes, as seen in Figure 7 (an updated graph of the data), begin with CIN I and are more prominent in the high grades of CIN (II, III) and cancer [39]. This appears to correlate CIS with the novel observations presented in the present study with respect to the increased expression of chromatin remodelling complex components indicating that these expression changes result in an alteration of the cell/nuclear phenotype.


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

Shadeo A, Chari R, Lonergan KM, Pusic A, Miller D, Ehlen T, Van Niekerk D, Matisic J, Richards-Kortum R, Follen M, Guillaud M, Lam WL, MacAulay C - BMC Genomics (2008)

An updated box plot from Guillaud et al. showing the correlation between a linear discriminant function score (Texture Score) based entirely on only texture phenotype features measured of the nuclei in formalin fixed quantitatively stained sections of biopsied tissue [39]. The error bars represent the 5th and 95th percentiles; the box represents the central 50th percentile and the solid square the mean of the distribution of the scores for measured sections with the noted histopathological diagnosis. The numbers over the boxes are the number of samples measured for the specific diagnosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2277413&req=5

Figure 7: An updated box plot from Guillaud et al. showing the correlation between a linear discriminant function score (Texture Score) based entirely on only texture phenotype features measured of the nuclei in formalin fixed quantitatively stained sections of biopsied tissue [39]. The error bars represent the 5th and 95th percentiles; the box represents the central 50th percentile and the solid square the mean of the distribution of the scores for measured sections with the noted histopathological diagnosis. The numbers over the boxes are the number of samples measured for the specific diagnosis.
Mentions: This differential expression in the chromatin remodelling genes could result in changes in the organization of the DNA. If these changes are large enough they could be detectable. Previously, we quantified changes in nuclear texture with increasing grade of CIN [39]. These measured phenotype changes, as seen in Figure 7 (an updated graph of the data), begin with CIN I and are more prominent in the high grades of CIN (II, III) and cancer [39]. This appears to correlate CIS with the novel observations presented in the present study with respect to the increased expression of chromatin remodelling complex components indicating that these expression changes result in an alteration of the cell/nuclear phenotype.

Bottom Line: Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Genetics & Developmental Biology, British Columbia Cancer Research Centre, Vancouver, BC, Canada. ashadeo@bccrc.ca.

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus