Successful cancer treatment is based on our understanding of a number of biological considerations such as its mechanisms for survival, evasion of tumor suppressor programs, and proliferation. Unfortunately, cancer evolution is often chaotic and a single tumor may exhibit many different methods for achieving its goals, such as direct mutation of tumor suppressor genes, over-expression of genes which target tumor suppressors, or both. With that in mind, it is crucial for clinicians and researchers to be able to distinguish the properties of each tumor and identify similarities between them, so that broad-impact treatments can be devised. Recently, a number of advances have been made which allow researchers to gather more detailed information in a high-throughput manner on the behavior of individual tumors. Where once only gross gene expression information could be gleaned using a microarray chip, now sequencing technology enables us to understand what individual isoforms of genes are being expressed, and in what abundance. Sequencing technology advances have also enabled us to find novel sites of expression on the genome which do not correspond to known proteins, and in fact provide evidence of a new class of large non-coding RNA molecules with functional consequences for cancer tumors. In this thesis, we present novel methodologies for the identification of alternative transcript as well as non-coding RNA usage in subgroups of breast cancer tumors using data from next generation transcriptome sequencing. Using these methods, we have identified genes which are differentially spliced between breast cancer tumors belonging to estrogen positive (ER+) and negative (ER-) sets, as well as in novel subgroups, and validated the existence of these transcripts in tumor tissue RNA using RT-PCR. Additionally, we present evidence of non-coding RNA transcripts which are aberrantly expressed based on estrogen status, and validate these in a similar way. These discoveries and new methodologies will help elucidate the biological differences between these subgroups of breast cancer, and will assist ongoing research into transcriptome abnormalities in other cancers as sequencing data become available.
Subject (authority = RUETD)
Topic
Computational Biology and Molecular Biophysics
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.