Skip to main content
Kent Academic Repository

Investigating neuroblastoma cell lines to identify mechanisms of resistance to cisplatin and vincristine

Hetland, Marit Andrea Klokkhammer (2017) Investigating neuroblastoma cell lines to identify mechanisms of resistance to cisplatin and vincristine. Master of Science by Research (MScRes) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.63943) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:63943)

PDF
Language: English

Restricted to Repository staff only
Contact us about this Publication
[thumbnail of 30MScR Thesis M.A.K. Hetland July 2017.pdf]
HTML (Appendix)
Language: English

Restricted to Repository staff only
Contact us about this Publication
[thumbnail of Appendix]
Official URL:
https://doi.org/10.22024/UniKent/01.02.63943

Abstract

Tumour relapse and acquired resistance formation to drugs are major complications in effective cancer treatment. Neuroblastoma is a heterogeneous malignancy of the sympathetic nervous system to which cisplatin and vincristine are two commonly used chemotherapeutic drugs. Many high-risk neuroblastomas are initially sensitive to therapy before acquiring resistance. Analysis of whole exome sequencing data from the MYCN-amplified neuroblastoma cell line UKF-NB-3, its cisplatin-adapted subline UKF-NB-3rCDDP1000, and its vincristine-adapted subline UKF-NB-3rVCR10 was performed with the aim of identifying and comparing resistance formation between

these two drugs that substantially differ in their mechanisms of action. 2,038 variants present only in the cisplatin-adapted subline, 122 variants present only in the vincristine-adapted subline and 50 variants overlapping the two drug-adapted sublines were identified as likely to have a functional effect on gene structure, function or expression. An over-representation analysis to identify enrichment of mutated genes in signalling pathways and gene ontology categories revealed several resistance mechanisms overlapping the drug-adapted sublines, related to prevention of the drugs from reaching their targets, through mutations in the extracellular matrix proteins, ABC transporters and solute carrier transporters. Nucleoporins, which regulate transport across the nuclear membrane, and calcium voltage-gated ion channel subunits, which are important in calcium homeostasis, were also highly mutated in the cisplatin-adapted subline, indicating possible roles in resistance formation. Mutations in MAP3K1, NOTCH2 and TP53 in the vincristine-adapted subline could confer resistance through evading pro-apoptotic signals. Several mechanisms related to olfactory receptors, mucin production and decreased contact inhibition overlapped the three cell lines, which could be due to the underlying genetics of the parental UKF-NB-3 cell line.

Item Type: Thesis (Master of Science by Research (MScRes))
DOI/Identification number: 10.22024/UniKent/01.02.63943
Additional information: The author of this thesis has requested that it be held under closed access. We are sorry but we will not be able to give you access or pass on any requests for access. 10/08/21
Uncontrolled keywords: Computational Biology; Neuroblastoma; Cell lines; Drug resistance
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 11 Oct 2017 09:10 UTC
Last Modified: 10 Aug 2021 07:06 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/63943 (The current URI for this page, for reference purposes)

University of Kent Author Information

Hetland, Marit Andrea Klokkhammer.

Creator's ORCID:
CReDIT Contributor Roles:
  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.