Advisory Committee Chair
Trygve O Tollefsbol
Advisory Committee Members
Molly S Bray
James A Coker
Document Type
Thesis
Date of Award
2012
Degree Name by School
Master of Science (MS) College of Arts and Sciences
Abstract
Neoplastic reprogramming generates cancerous cells from normal derivatives, enabling researchers to create a model of the early stages of oncogenesis and analyze molecular changes in real-time. Aberrations in DNA methylation are considered a major mechanism contributing to the acquisition and maintenance of a cancerous phenotype; however, little research exists regarding gene-specific changes in DNA methylation during the transition from a normal to neoplastic cell. Human mammary epithelial cells (HMECs) underwent neoplastic transformation through the addition of three defined genetic elements to generate one line of semi-transformed, pre-malignant cells (SHMECs) and two separate lines of fully transformed, malignant cells (THMECs). We used an Illumina Infinium HumanMethylation27 BeadChip to interrogate 27,578 CpG loci and identify genes that exhibited differential methylation over three consecutive time points during breast tumorigenesis. We found 805 CpG loci exhibiting a single DNA methylation change from SHMEC to THMECs at 40 days (THMEC-40d). These genes were enriched for biological functions associated with cellular growth and proliferation. In contrast, 196 CpG sites were differentially methylated between THMEC-40d and THMEC-80d and were associated with major developmental processes. The data generated provide novel insight into the both the timing and possible role of specific DNA methylation changes throughout the initiation and progression of breast oncogenesis. However, additional studies are necessary to fully explore how these specific DNA methylation alterations, in addition to other epigenetic aberrations, mechanistically contribute to differential gene and protein expression, enabling the development of breast cancer.
Recommended Citation
Mitchell, Natalie E., "Genome-Wide DNA Methylation Changes During Breast Tumorigenesis" (2012). All ETDs from UAB. 2482.
https://digitalcommons.library.uab.edu/etd-collection/2482