Supervisors info:
Δρ. Χρήστος Κοντός Επίκουρος Καθηγητής Τμήμα Βιολογίας ΕΚΠΑ, (Επιβλέπων),
Δρ. Θεόδωρο Ράμπια Ερευνητή Γ’ ,ΙΙΒΕΑΑ (Συνεπιβλέπων)
Summary:
Melanoma, the most aggressive form of skin cancer, is characterized by its high metastatic potential and is often associated with genetic alterations affecting critical cellular pathways. Recent studies have highlighted the importance of translational fidelity loss in oncogenesis and melanoma progression. Translational fidelity, referring to the accuracy of protein synthesis, when disrupted in cancer cells, can lead to the production of defective proteins that promote tumor growth, resistance to therapies, and metastasis. Previous studies, following meta-analysis of gene sequencing data, have demonstrated that the inactivation of the mismatch repair (MMR) pathway is correlated with the accumulation of harmful mutations in four genes encoding aminoacyl-tRNA synthetases (aaRS) in TCGA patient samples from the Pan Cancer Atlas. In the present thesis, a meta-analysis was conducted on data from TCGA Pan Cancer Atlas Skin Cutaneous Melanoma (SKCM) patients who present co-localized mutations in both MMR pathway genes (POLE, POLD1, MLH1, MLH3, MSH2, MSH3, MSH6, PMS1, PMS2) and four genes encoding aminoacyl-tRNA synthetases (LARS1, EPRS1, VARS1, RARS1). The study focused on patients with point mutations in critical regions of aminoacyl-tRNA synthetases, with the aim of analyzing their impact on the structural integrity of these molecules. The analysis of these mutations and their categorization as damaging or non-damaging will form the basis for future modeling of critical mutations in cancer cell lines and testing, using reference genes, whether critical mutations in aminoacyl-tRNA synthetase molecules can lead to a loss of translational fidelity.
Keywords:
Melanoma, Deregulation of Translation Fidelity, aminoacyl-tRNA syntetases,Mismatch Repair Pathway,LARS1,VARS1,EPRS1,RARS1
