Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Gene fusions and microRNAs in cancer

Hafstað, Völundur LU (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
The genome of cancer cells is unstable. Flaws in the DNA repair mechanisms of these cells can lead to the creation of gene fusions, where parts of two different genes are erroneously combined. Additionally, the expression of microRNAs (miRNAs), small regulatory molecules that control gene activity, is often dysregulated in cancer. In this thesis, we investigate miRNAs, gene fusions, and the interplay between the two in cancer using bioinformatic approaches. We found that miRNA host genes are common in gene fusions and may provide an alternative mechanism to dysregulate their expression. Since gene fusion detection methods are prone to errors, we developed a method to validate fusion transcripts at the genomic level using matched... (More)
The genome of cancer cells is unstable. Flaws in the DNA repair mechanisms of these cells can lead to the creation of gene fusions, where parts of two different genes are erroneously combined. Additionally, the expression of microRNAs (miRNAs), small regulatory molecules that control gene activity, is often dysregulated in cancer. In this thesis, we investigate miRNAs, gene fusions, and the interplay between the two in cancer using bioinformatic approaches. We found that miRNA host genes are common in gene fusions and may provide an alternative mechanism to dysregulate their expression. Since gene fusion detection methods are prone to errors, we developed a method to validate fusion transcripts at the genomic level using matched whole-genome sequencing data. Utilizing information on validated fusion events from 910 tumors in The Cancer Genome Atlas, we trained a machine learning classifier to predict which fusion event are real, and demonstrated that this approach can improve the quality of fusion detection. Finally, we investigated the function of the ERBB2-encoded mir-4728 in breast cancer at the transcriptional and translational level, and found that it impacts the level of aromatase and other genes involved in estrogen biosynthesis. These
findings contribute to a growing understanding of the complex nature of the cancer
genome. The papers in this thesis lay a groundwork for further exploration of the
multifaceted roles of both miRNAs and gene fusions in cancer, underscoring the
importance of continued investigation into their roles in cancer initiation, progression, and therapeutic response. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor, PhD Sandelin, Albin, Section for Computational and RNA Biology, Department of Biology & Biotech Research and Innovation Centre, Copenhagen University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
MicroRNAs, Gene fusions, Cancer, Molecular genetics, Bioinformatics
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:83
pages
84 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund
defense date
2024-06-13 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-578-7
language
English
LU publication?
yes
id
db31ae36-f686-4391-b781-62c986b32c14
date added to LUP
2024-05-16 08:53:58
date last changed
2024-05-23 08:52:18
@phdthesis{db31ae36-f686-4391-b781-62c986b32c14,
  abstract     = {{The genome of cancer cells is unstable. Flaws in the DNA repair mechanisms of these cells can lead to the creation of gene fusions, where parts of two different genes are erroneously combined. Additionally, the expression of microRNAs (miRNAs), small regulatory molecules that control gene activity, is often dysregulated in cancer. In this thesis, we investigate miRNAs, gene fusions, and the interplay between the two in cancer using bioinformatic approaches. We found that miRNA host genes are common in gene fusions and may provide an alternative mechanism to dysregulate their expression. Since gene fusion detection methods are prone to errors, we developed a method to validate fusion transcripts at the genomic level using matched whole-genome sequencing data. Utilizing information on validated fusion events from 910 tumors in The Cancer Genome Atlas, we trained a machine learning classifier to predict which fusion event are real, and demonstrated that this approach can improve the quality of fusion detection. Finally, we investigated the function of the ERBB2-encoded mir-4728 in breast cancer at the transcriptional and translational level, and found that it impacts the level of aromatase and other genes involved in estrogen biosynthesis. These<br/>findings contribute to a growing understanding of the complex nature of the cancer<br/>genome. The papers in this thesis lay a groundwork for further exploration of the<br/>multifaceted roles of both miRNAs and gene fusions in cancer, underscoring the<br/>importance of continued investigation into their roles in cancer initiation, progression, and therapeutic response.}},
  author       = {{Hafstað, Völundur}},
  isbn         = {{978-91-8021-578-7}},
  issn         = {{1652-8220}},
  keywords     = {{MicroRNAs; Gene fusions; Cancer; Molecular genetics; Bioinformatics}},
  language     = {{eng}},
  number       = {{2024:83}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Gene fusions and microRNAs in cancer}},
  url          = {{https://lup.lub.lu.se/search/files/183597612/V_lundur_Hafsta_-_WEBB.pdf}},
  year         = {{2024}},
}