EN
TÜRKÇE
Poster - 73
Mitochondrial Genetic Markers in Neuroblastoma: A Systematic Review of Their Role in Tumor Progression, Prognosis and Therapeutic Potential
Jyoti Sharma, Prabudh Goel, VIshesh Jain, Devendra Kumar Yadav, Anjan Kumar Dhua, Sandeep Agarwala
All India Institute of Medical Sciences, New Delhi
Background
Neuroblastoma (NB) is a highly aggressive pediatric malignancy accounting for a significant proportion of childhood cancer-related deaths. Despite intensive multimodal therapy, outcomes remain poor in high-risk cases. Emerging evidence highlights mitochondrial dysfunction as a key player in NB pathogenesis, influencing tumor metabolism, apoptosis resistance, and therapeutic response.
Objective
This systematic review aims to evaluate mitochondrial genetic alterations including mitochondrial DNA (mtDNA) mutations, mitochondria-associated proteins (MAPs), and mitochondria-related genes (MRGs) and assess their relevance to NB progression, prognosis, and therapeutic targeting.
Methods
A comprehensive search was conducted in PubMed for studies published from 2015 to 2024, following PRISMA guidelines. Studies involving genetic, transcriptomic, or proteomic profiling of mitochondrial alterations in NB were included. Reviews, case reports, and studies lacking NB-specific mitochondrial data were excluded. Data extraction and quality assessment were conducted independently by two reviewers.
Results
Eight studies met the inclusion criteria, analyzing 5,826 NB patients, 15,634 controls, and 70 NB cell lines. Recurrent mtDNA mutations, including variants in MT-ND4, MT-ND5, and MT-CYB (e.g., rs2853493, rs2853499), were associated with NB susceptibility. Transcriptomic data revealed over 1,700 MAP genes implicated in tumor progression, with scoring models (mtScore, mtRisk) effectively predicting prognosis. Functional studies highlighted mitochondrial metabolic reprogramming—such as the Warburg effect, impaired OXPHOS, and MERCS dysfunction contributing to chemoresistance. Therapeutic targets like FEN1, LETM1, MTCH2, and VDAC1 showed potential in sensitizing NB cells to apoptosis.
Conclusion
Mitochondrial genetic alterations significantly influence neuroblastoma biology and offer promising biomarkers and therapeutic targets. Further research is needed to validate these findings and explore mitochondrial-targeted treatment strategies in clinical settings.