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IDENTIFICATION OF CANDIDATE DNA METHYLATION MARKERS IN
DIFFUSE LARGE B-CELL LYMPHOMA
by
Brian Lee Pike
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 AND MOLECULAR BIOLOGY)
December 2006
Copyright 2006 Brian Lee Pike
Object Description
| Title | Identification of DNA methylation markers in diffuse large B-cell lymphoma |
| Author | Pike, Brian Lee |
| Author email | bpike@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2006-01-26 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-09-29 |
| Advisor (committee chair) | Hacia, Joseph G. |
| Advisor (committee member) |
Laird, Peter W. Frenkel, Baruch |
| Abstract | Clinically distinct subtypes of Diffuse Large B Cell Lymphoma (DLBCL) have gene expression profiles that reflect their origins from specific stages of B-cell maturation. We conducted epigenetic analyses to evaluate the DNA methylation status of CpG islands in germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL subtypes. Using two different platforms, we uncovered gene-associated CpG islands whose DNA methylation levels varied among DLBCL. Of these, the methylation levels of CpG islands proximal to ONECUT2 and FLJ21062 (HIC3) correlated with subtype identity. Interestingly, ONECUT2 is involved regulating TGF-beta signaling pathways crucial for B cell maturation. In contrast to expectations based on the two-hit hypothesis, ONECUT2 resides on a frequently amplified, instead of deleted, genomic segment in DLBCL. This novel observation may reflect a mechanism for silencing potential tumor suppressor genes present in large, amplified genomic regions. Overall, these results suggest that DNA methylation may prove to be valuable for the identification and early detection of cancers derived from closely related cell lineages. |
| Keyword | cancer; lymphoma; germinal center; DNA methylation; biomarker |
| 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 |
| Type | texts |
| Legacy record ID | usctheses-m57 |
| Rights | Pike, Brian Lee |
| 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-Pike-20060929 |
| Archival file | uscthesesreloadpub_Volume17/etd-Pike-20060929.pdf |
Description
| Title | Page 1 |
| Full text | IDENTIFICATION OF CANDIDATE DNA METHYLATION MARKERS IN DIFFUSE LARGE B-CELL LYMPHOMA by Brian Lee Pike 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 AND MOLECULAR BIOLOGY) December 2006 Copyright 2006 Brian Lee Pike |
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