Exploring the Role of the ATRX Gene in High-Risk Neuroblastoma via Genome Engineering Techniques
Typ
Examensarbete för masterexamen
Master's Thesis
Master's Thesis
Program
Biotechnology (MPBIO), MSc
Publicerad
2023
Författare
Jafargholizadeh, Setareh
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Neuroblastoma (NB) is a rare but aggressive pediatric cancer originating form the
embryonic neural crest cells. Abnormal telomere maintenance has been implicated as a
major cause of high-risk neuroblastoma, with a subset of tumors following the
Alternative Lengthening of Telomere positive (ALT+) pathway. ALT+ tumors are
difficult to treat due to their resistance to therapy. The exact cause of NB remains
unclear, but recent research suggests genetic mutations as a possible cause, particularly
mutations in the ATRX gene observed in ALT+ NB patients. This study focuses on
understanding the role of the ATRX gene, in promoting ALT+ neuroblastoma. To
investigate this, a dual approach was utilized, involving CRISPR/Cas9 technology for
complete ATRX knockout and lentiviral shRNA silencing to reduce ATRX expression.
The gene expression of ATRX has been successfully downregulated, but the successful
knockout of ATRX could not be verified using CRISPR/Cas9 methods. Hence,
additional validation is necessary to assess the impact of ATRX expression on ALT+ and
to develop more effective strategies for addressing this subgroup of high-risk
neuroblastoma (NB).
Beskrivning
Ämne/nyckelord
Neuroblastoma , Lentiviral vector , ATRX , CRISPR/Cas9