A genomic analysis of NKX2-1-driven oncogenesis in non-small cell lung cancer

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Abstract/Contents

Abstract
Human cancer is a complex set of diseases, but as the tools and techniques of genomic analysis expand, each newly explored cancer genome furthers our understanding of the genetic factors that drive and sustain malignant cells. In the case of lung cancer, many efforts are being made to define the mechanisms by which specific genetic alterations drive the oncogenic activity of these malignancies. Genomic analysis studies have uncovered a focal amplification located at the cytoband 14q13.3 in the adenocarcinoma subtype of non-small cell lung cancer (NSCLC). The minimal 14q13.3 amplicon includes NKX2-1, a homeobox transcription factor that plays a crucial role in lung organogenesis. Preliminary studies with NKX2-1 have revealed that the overexpression of the protein secondary to gene amplification in lung adenocarcinoma creates a context-specific, or, alternatively, a "lineage-dependent", environment in which NKX2-1 becomes essential for tumor cell line survival when expressed outside of its normal developmental context. While there is unequivocal evidence that NKX2-1 is crucial for the survival of lung adenocarcinoma cell lines with the 14q13.3 amplification, its mechanism of action has yet to be fully deduced. The work presented in this dissertation focuses on uncovering the mechanisms by which NKX2-1 drives proliferation and survival of a subset of NSCLC tumors.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2014
Issuance monographic
Language English

Creators/Contributors

Associated with Clarke, Nicole
Associated with Stanford University, Cancer Biology Program.
Primary advisor Pollack, Jonathan R
Thesis advisor Pollack, Jonathan R
Thesis advisor Morrison, Ashby J
Thesis advisor Sweet-Cordero, Eric
Thesis advisor West, Robert
Advisor Morrison, Ashby J
Advisor Sweet-Cordero, Eric
Advisor West, Robert

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Nicole Clarke.
Note Submitted to the Interdisciplinary Cancer Biology Program.
Thesis Thesis (Ph.D.)--Stanford University, 2014.
Location electronic resource

Access conditions

Copyright
© 2014 by Nicole Clarke
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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