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Genomic characterization of non-small cell lung cancer - clinical and molecular implications

Karlsson, Anna F LU (2018)
Abstract (Swedish)
Lung cancer accounts for 1.6 million cancers annually and 1.3 million deaths per year make the disease the deadliest type of cancer. Smoking is the most prominent cause. High mortality rates are partly due to late diagnosis which limits the therapy options. Improved understanding of molecular and biological mechanisms of tumor development could guide current therapy selection or pave way for novel therapies. The aim of this thesis is to characterize non-small cell lung cancer (NSCLC) genomes, stratifying tumors and patient groups with the intent of improved therapeutic options. A framework for treatment predictive mutation testing was established and, in parallel, the NanoString technology was evaluated for fusion gene detection. In an... (More)
Lung cancer accounts for 1.6 million cancers annually and 1.3 million deaths per year make the disease the deadliest type of cancer. Smoking is the most prominent cause. High mortality rates are partly due to late diagnosis which limits the therapy options. Improved understanding of molecular and biological mechanisms of tumor development could guide current therapy selection or pave way for novel therapies. The aim of this thesis is to characterize non-small cell lung cancer (NSCLC) genomes, stratifying tumors and patient groups with the intent of improved therapeutic options. A framework for treatment predictive mutation testing was established and, in parallel, the NanoString technology was evaluated for fusion gene detection. In an expansion of the fusion gene detection method, we included the possibility for simultaneous prediction of NSCLC histology, i.e. a multicomponent assay, applicable to tissue amounts used in standard clinical diagnostics. As accurate distinction of the histological subtypes is crucial for clinical management of lung cancer, the World Health Organization (WHO) administer and continuously update guidelines for histological classification. The mutational and transcriptional findings of this thesis work support their 2015 revision of histological subgroups. In addition, comprehensive global methylation analysis of lung cancer was performed, resulting in the detection of five epigenetically distinct groups of lung tumors associated with histology, gene expression, copy number variation and survival. In summary, this thesis has focused on genomic characterization of NSCLC, contributing to molecular findings and clinical implications. (Less)
Abstract
Lung cancer accounts for 1.6 million cancers annually and 1.3 million deaths per year make the disease the deadliest type of cancer. Smoking is the most prominent cause. High mortality rates are partly due to late diagnosis which limits the therapy options. Improved understanding of molecular and biological mechanisms of tumor development could guide current therapy selection or pave way for novel therapies. The aim of this thesis is to characterize non-small cell lung cancer (NSCLC) genomes, stratifying tumors and patient groups with the intent of improved therapeutic options. A framework for treatment predictive mutation testing was established and, in parallel, the NanoString technology was evaluated for fusion gene detection. In an... (More)
Lung cancer accounts for 1.6 million cancers annually and 1.3 million deaths per year make the disease the deadliest type of cancer. Smoking is the most prominent cause. High mortality rates are partly due to late diagnosis which limits the therapy options. Improved understanding of molecular and biological mechanisms of tumor development could guide current therapy selection or pave way for novel therapies. The aim of this thesis is to characterize non-small cell lung cancer (NSCLC) genomes, stratifying tumors and patient groups with the intent of improved therapeutic options. A framework for treatment predictive mutation testing was established and, in parallel, the NanoString technology was evaluated for fusion gene detection. In an expansion of the fusion gene detection method, we included the possibility for simultaneous prediction of NSCLC histology, i.e. a multicomponent assay, applicable to tissue amounts used in standard clinical diagnostics. As accurate distinction of the histological subtypes is crucial for clinical management of lung cancer, the World Health Organization (WHO) administer and continuously update guidelines for histological classification. The mutational and transcriptional findings of this thesis work support their 2015 revision of histological subgroups. In addition, comprehensive global methylation analysis of lung cancer was performed, resulting in the detection of five epigenetically distinct groups of lung tumors associated with histology, gene expression, copy number variation and survival. In summary, this thesis has focused on genomic characterization of NSCLC, contributing to molecular findings and clinical implications. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • M.D, Ph.D. Brustugun, Odd-Terje, The Norwegian Radium Hospital, Oslo, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Lung cancer, histology, non-small cell lung cancer, gene expression, gene fusion, Methylation
pages
89 pages
publisher
Lund University, Faculty of Medicine
defense location
Onkologiklinikens föreläsningssal, Klinikgatan 5, Skånes Universitetssjukhus i Lund
defense date
2018-10-19 09:00
ISBN
978-91-7619-690-8
language
English
LU publication?
yes
id
a2a0a480-966e-470e-838b-8643a20dbcf5
date added to LUP
2018-09-19 20:51:22
date last changed
2018-11-26 07:26:27
@phdthesis{a2a0a480-966e-470e-838b-8643a20dbcf5,
  abstract     = {Lung cancer accounts for 1.6 million cancers annually and 1.3 million deaths per year make the disease the deadliest type of cancer. Smoking is the most prominent cause. High mortality rates are partly due to late diagnosis which limits the therapy options. Improved understanding of molecular and biological mechanisms of tumor development could guide current therapy selection or pave way for novel therapies. The aim of this thesis is to characterize non-small cell lung cancer (NSCLC) genomes, stratifying tumors and patient groups with the intent of improved therapeutic options. A framework for treatment predictive mutation testing was established and, in parallel, the NanoString technology was evaluated for fusion gene detection. In an expansion of the fusion gene detection method, we included the possibility for simultaneous prediction of NSCLC histology, i.e. a multicomponent assay, applicable to tissue amounts used in standard clinical diagnostics. As accurate distinction of the histological subtypes is crucial for clinical management of lung cancer, the World Health Organization (WHO) administer and continuously update guidelines for histological classification. The mutational and transcriptional findings of this thesis work support their 2015 revision of histological subgroups. In addition, comprehensive global methylation analysis of lung cancer was performed, resulting in the detection of five epigenetically distinct groups of lung tumors associated with histology, gene expression, copy number variation and survival. In summary, this thesis has focused on genomic characterization of NSCLC, contributing to molecular findings and clinical implications.},
  author       = {Karlsson, Anna F},
  isbn         = {978-91-7619-690-8},
  keyword      = {Lung cancer,histology,non-small cell lung cancer,gene expression,gene fusion,Methylation},
  language     = {eng},
  pages        = {89},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  title        = {Genomic characterization of non-small cell lung cancer - clinical and molecular implications},
  year         = {2018},
}