A Functional Investigation of the Frequently Mutated Splicing Factor U2AF1 in Non-Small Cell Lung Cancer

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Abstract/Contents

Abstract: RNA splicing is a critical step in manufacturing most human proteins. Regulating the splicing machinery is crucial for normal development, and aberrant splicing can result in diseases such as cancer. Recent studies have uncovered a recurrent mutation of the splicing factor U2AF1 in several human cancers including lung cancer. The lung cancer cell line HCC78 is the only cancer cell line known to harbor this mutation, and it also has a gene fusion involving the ROS1 gene that genetically separates it from other types of lung cancer. This study sets out to both examine splicing effects of the mutated U2AF1 in lung cancer and to clarify the relationship between mutant U2AF1 and the ROS1-fusion, two rare genetic alterations that have been observed to occur together in lung cancers at a significantly higher than expected frequency. Specifically, by genomically editing the HCC78 cell line and repairing the U2AF1 point mutation, an appropriate point of comparison has been created using transcription activator-like effector nucleases (TALENs). Use of TALENs allows for targeting sequence-specific locations in the genome for double-stranded breaks. Taking advantage of endogenous DNA repair machinery, a designed sequence has been inserted into the genome of these HCC78 cells to repair the U2AF1 point mutation.

Type of resource	text
Date created	May 2014

Author	Ishisoko, Noriko
Primary advisor	Diehn, Maximilian
Degree granting institution	Stanford University. Department of Bioengineering.

Location	https://purl.stanford.edu/db839kj8742

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License: This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

Preferred Citation: Ishisoko, Noriko (2014). A Functional Investigation of the Frequently Mutated Splicing Factor U2AF1 in Non-Small Cell Lung Cancer. Stanford Digital Repository. Available at: http://purl.stanford.edu/db839kj8742

Undergraduate Theses, School of Engineering

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