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Mechanisms Leading to Chromosomal Instability in Oral Cancer Cells

Reshmi, Shalini C (2005) Mechanisms Leading to Chromosomal Instability in Oral Cancer Cells. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

In the United States, cancer is a leading cause of death, second only to heart disease (MOKDAD et al. 2004). Although it is estimated that in 2005, cancer of the oral cavity will account for only 2.1% of cancer cases and 1.3% of overall cancer deaths in the U. S. (JEMAL et al. 2005), high-risk behaviors such as smoking cigarettes, using smokeless tobacco, and consuming excessive alcohol have been shown to play a major role in OSCC development. Exposure to environmental agents, including tobacco products, alcoholic beverages, and/or viruses, such as human papillomavirus (FORASTIERE et al. 2001; HO and CALIFANO 2004; MORK et al. 2001) have a profound influence on cells within the oral cavity. These factors have been shown to induce genetic alterations including chromosomal alterations, DNA changes, and/or epigenetic alterations, such as changes in DNA methylation that affect genetic regulation. Genetic alterations in cells are useful biological markers that assist in early detection of cancer and response to therapy (SIDRANSKY 1995). Currently, however, there are no useful biomarkers to identify early changes involved in OSCC development. One genetic alteration observed in 45% of OSCC is amplification of chromosomal band, 11q13. This event has been shown to follow dysplastic cellular changes, but occur prior to development of carcinoma in situ (FORASTIERE et al. 2001). Therefore, 11q13 amplification may be a useful biomarker for detecting OSCC. In addition, understanding the molecular mechanisms that promote 11q13 gene amplification may provide valuable information for devising novel prevention measures and therapies. In the current study, we show that the primary mechanism promoting 11q13 gene amplification is BFB cycles. Furthermore, we suggest that breakage at the common fragile site, FRA11F, may be responsible for initiating 11q13 gene amplification. By determining the primary mechanism that leads to 11q13 amplification in OSCC, additional investigations focusing on the biological basis of this process may provide important information for developing successful measures and treatments that will increase the survival rate for individuals afflicted with oral cancer.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Reshmi, Shalini Cshalini.reshmi@hgen.pitt.edu
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairGollin, Susanne Msgollin@hgen.pitt.eduGOLLIN
Committee MemberRowley, Janet Djrowley@medicine.bsd.uchicago.edu
Committee MemberZhang, Linzhanglx@upmc.eduLIZ22
Committee MemberSurti, Urvashiusurti@mail.magee.edu
Committee MemberSaunders, William Swsaund@pitt.eduWSAUND
Date: 5 July 2005
Date Type: Completion
Defense Date: 17 March 2005
Approval Date: 5 July 2005
Submission Date: 14 April 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: chromosomal instability; fragile sites; gene amplification; anaphase bridges; oral cancer; breakage-fusion-bridge cycles
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04142005-163803/, etd-04142005-163803
Date Deposited: 10 Nov 2011 19:37
Last Modified: 19 Dec 2016 14:35
URI: http://d-scholarship.pitt.edu/id/eprint/7147

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