Discovery and characterization of novel somatic and widespread inherited polymorphic fusion genes in humans /

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Bibliographic Details
Author / Creator:Bandlamudi, Chaitanya, author.
Imprint:2016.
Ann Arbor : ProQuest Dissertations & Theses, 2016
Description:1 electronic resource (222 pages)
Language:English
Format: E-Resource Dissertations
Local Note:School code: 0330
URL for this record:http://pi.lib.uchicago.edu/1001/cat/bib/10773441
Hidden Bibliographic Details
Other authors / contributors:University of Chicago. degree granting institution.
ISBN:9781339564715
Notes:Includes supplementary digital materials.
Advisors: Kevin P. White Committee members: Michelle M. Le Beau; Dan L. Nicolae; Andrey Rzhetsky.
This item is not available from ProQuest Dissertations & Theses.
Dissertation Abstracts International, Volume: 77-08(E), Section: B.
English
Summary:Fusion genes have played a seminal role in cancer biology both clinically as well as substantially promoting our understanding of the mechanisms in cancer. Although fusions genes have been studied primarily in the context of cancer, the shared DNA repair mechanisms between mitotic and meiotic cells suggests that such events may exist as polymorphic events in healthy populations. In chapter 1, I present a comprehensive overview of our understanding of somatic as well as germline gene fusions. In chapter 2, I present a new fusion discovery method that is central to the discoveries in my research. In chapter 3, I survey nearly ten thousand cancer patients across various tumor types and study the pan-cancer characteristics of fusions. I identify some of the most recurrently identified novel fusions and followup with functional validations to investigate their tumorigenic properties. In chapter 4, I surveyed more than five hundred healthy individuals and discovered many novel polymorphic fusion genes. I show that a substantial proportion of the recurrent polymorphic fusion genes display population specific differentiation. Using gene expression profiles, I demonstrate that many of these fusion genes may have functional consequences. This previously unreported class of genetic variation may have far reaching implications in explaining a proportion of missing heritability. In the final chapter, I will discuss the key findings and highlight several future directions that will further our understanding of the role of gene fusions in both cancer as well as healthy individuals.
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520 |a Fusion genes have played a seminal role in cancer biology both clinically as well as substantially promoting our understanding of the mechanisms in cancer. Although fusions genes have been studied primarily in the context of cancer, the shared DNA repair mechanisms between mitotic and meiotic cells suggests that such events may exist as polymorphic events in healthy populations. In chapter 1, I present a comprehensive overview of our understanding of somatic as well as germline gene fusions. In chapter 2, I present a new fusion discovery method that is central to the discoveries in my research. In chapter 3, I survey nearly ten thousand cancer patients across various tumor types and study the pan-cancer characteristics of fusions. I identify some of the most recurrently identified novel fusions and followup with functional validations to investigate their tumorigenic properties. In chapter 4, I surveyed more than five hundred healthy individuals and discovered many novel polymorphic fusion genes. I show that a substantial proportion of the recurrent polymorphic fusion genes display population specific differentiation. Using gene expression profiles, I demonstrate that many of these fusion genes may have functional consequences. This previously unreported class of genetic variation may have far reaching implications in explaining a proportion of missing heritability. In the final chapter, I will discuss the key findings and highlight several future directions that will further our understanding of the role of gene fusions in both cancer as well as healthy individuals. 
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