Using integrative genomic approaches to understand the biology of pancreatic cancer

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Abstract/Contents

Abstract
Pancreatic ductal adenocarcinoma, subsequently referred to as pancreatic cancer, is one of the most deadly cancers with a five-year survival of only 5%. Typical treatment regimens include surgery and chemotherapy while targeted therapies are lacking. A better understanding of the underlying cancer biology may yield novel therapeutic targets. The field of genomics has transformed our ability to study cancer. Over the past two decades, microarray and sequencing based innovations have enabled biology to be carried out at the --omic scale (discussed further in Chapter 1). This dissertation employs --omic level analysis to query the differences between the pancreatic cancer genome and the normal human genome. First, high throughput structural characterizations were performed in order to annotate the mutated, rearranged, deleted, and amplified genes across seventy pancreatic cancers. These assays identified hundreds of candidate cancer genes. Among these candidates, SMURF1 was validated to be an oncogene (Chapter 2). Furthermore, various subunits of the SWI/SNF chromatin remodeling complex were validated to be tumor suppressor genes (Chapter 3). While SMURF1 and SWI/SNF were validated individually, the other candidates from structural studies were evaluated in parallel shRNA competive growth screen. From this, we characterize nine genes further -- some previously known to play a role in cancer and some novel (Chapter 4). The sum total of all of this work is a much deeper understanding of the biology of pancreatic cancer, yielding many novel therapeutic targets and hopefully allowing scientists to gain a foothold in the fight against this disease.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2012
Issuance monographic
Language English

Creators/Contributors

Associated with Shain, Alan Hunter
Associated with Stanford University, Cancer Biology Program.
Primary advisor Pollack, Jonathan D
Thesis advisor Pollack, Jonathan D
Thesis advisor Chang, Howard
Thesis advisor Lipsick, Joseph Steven, 1955-
Thesis advisor Lowe, Anson W
Advisor Chang, Howard
Advisor Lipsick, Joseph Steven, 1955-
Advisor Lowe, Anson W

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Alan Hunter Shain.
Note Submitted to the Interdisciplinary Cancer Biology Program.
Thesis Ph.D. Stanford University 2012
Location electronic resource

Access conditions

Copyright
© 2012 by Alan Hunter Shain
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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