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DEVELOPMENT OF DNA METHYLATION BASED BIOMARKERS FOR THE
EARLY DETECTION OF SQUAMOUS CELL LUNG CANCER.
by
Paul P. Anglim
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY & MOLECULAR BIOLOGY)
December 2008
Copyright 2008 Paul Anglim
Object Description
| Title | Development of DNA methylation based biomarkers for the early detection of squamous cell lung cancer |
| Author | Anglim, Paul P. |
| Author email | anglim@usc.edu; paulanglim@verizon.net |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-07-24 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-12-08 |
| Advisor (committee chair) | Laird-Offringa, Ite A. |
| Advisor (committee member) |
Johnson, Deborah Rice, Judd Siegmund, Kimberly |
| Abstract | Lung cancer is the number one cancer killer in the United States. This disease is divided into two sub-types, small cell lung cancer, (10-15% of lung cancer cases), and non-small cell lung cancer (NSCLC; 85-90% of cases). As NSCLC is the more common and less aggressive sub-type, its early detection has very high potential for saving lives. No routine screening method that facilitates early detection exists, and this is likely the reason for the high mortality rate of this disease. Imaging and cytology based screening strategies have been employed for early detection, and while some are sensitive, none has been demonstrated to reduce lung cancer mortality. Developing specific molecular markers that can compliment imaging techniques may facilitate a reduction in lung cancer mortality. DNA methylation has emerged as a highly promising biomarker, and is studied in multiple cancers.; NSCLC is further subdivided into four histological subtypes, each with its own molecular profile. The goal of our work is to develop sensitive and specific DNA methylation-based markers for early detection of squamous (SQ) lung cancer, which accounts for 30% of all lung cancer cases. Using a combination of MethyLight and the high-throughput DNA methylation analysis platform the GoldenGate assay, we identified a 10-panel with high specificity (92.6%) for detection of SQ lung cancer. that used in concert with sensitive imaging techniques may facilitate early detection of SQ lung cancer. We further characterized the reproducibility of the GoldenGate assay, and determined that we can obtain high quality data using DNA from FFPE tissue. |
| Keyword | lung cancer; early detection; squamous; DNA methylation |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1889 |
| Rights | Anglim, Paul P. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Anglim-2548 |
| Archival file | uscthesesreloadpub_Volume48/etd-Anglim-2548.pdf |
Description
| Title | Page 1 |
| Full text | DEVELOPMENT OF DNA METHYLATION BASED BIOMARKERS FOR THE EARLY DETECTION OF SQUAMOUS CELL LUNG CANCER. by Paul P. Anglim A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY & MOLECULAR BIOLOGY) December 2008 Copyright 2008 Paul Anglim |
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