Master thesis presentation: Setareh Jafargholizadeh, MPBIO

Examiner: Yvonne Nygård
Supervisor: Tanmoy Mondal

Opponent: Hanna Tranchell

Abstract:

Neuroblastoma (NB) is a rare but aggressive pediatric cancer originating from 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. We have successfully downregulated the gene expression of ATRX but the successful knockout of the 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).