BACKGROUND: Molecular aberrations occurring in primary ovarian clear cell carcinoma (OCCC) can be of diagnostic, predictive, and prognostic significance. However, a complex molecular study including genomic and transcriptomic analysis of large number of OCCC has been lacking. METHODS: 113 pathologically confirmed primary OCCCs were analyzed using capture DNA NGS (100 cases; 727 solid cancer related genes) and RNA-Seq (105 cases; 147 genes) in order to describe spectra and frequency of genomic and transcriptomic alterations, as well as their prognostic and predictive significance. RESULTS: The most frequent mutations were detected in genes ARID1A, PIK3CA, TERTp, KRAS, TP53, ATM, PPP2R1A, NF1, PTEN, and POLE (51,47,27,18,13,10,7,6,6, and 4%, respectively). TMB-High cases were detected in 9% of cases. Cases with POLEmut and/or MSI-High had better relapse-free survival. RNA-Seq revealed gene fusions in 14/105 (13%) cases, and heterogeneous expression pattern. The majority of gene fusions affected tyrosine kinase receptors (6/14; four of those were MET fusions) or DNA repair genes (2/14). Based on the mRNA expression pattern, a cluster of 12 OCCCs characterized by overexpression of tyrosine kinase receptors (TKRs) AKT3, CTNNB1, DDR2, JAK2, KIT, or PDGFRA (p < 0.00001) was identified. CONCLUSIONS: The current work has elucidated the complex genomic and transcriptomic molecular hallmarks of primary OCCCs. Our results confirmed the favorable outcomes of POLEmut and MSI-High OCCC. Moreover, the molecular landscape of OCCC revealed several potential therapeutical targets. Molecular testing can provide the potential for targeted therapy in patients with recurrent or metastatic tumors.

• MeSH
• adenokarcinom z jasných buněk * genetika   MeSH
• fúze genů MeSH
• genomika MeSH
• lidé MeSH
• lokální recidiva nádoru * MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The most frequent alterations in glioblastomas are mutations and deletions of the tumour suppressor genes PTEN and p53 and amplification of epidermal growth factor receptor (EGFR) and platelet derived growth factor receptor (PDGFR). The aim of the project is 1)verification of PTEN influence on the inhibition of glioma cell lines proliferation, 2)analysis of PTEN influence on the expression of proteins regulating PI3-K/PKB/Akt, MAPK pathways, cell cycle and thrombpspondin 1. 3)analysis of the relationship between PTEN expression and expression of proteins regulating PI3-K/PKB/Akt, MAPK pathways, cell cycle and thrombospondin 1 in the collection of samples from low grade and high grade astroglial tumours. For experiments we plan to use these methods: cell culture cultivation, transfection of DNA, detection of cell proliferation, protein electrophoresis, Western blot analysis, immunocytochemistry and immunohistochemistry.

Mezi nejčastější genetické alterace spojené se vznikem glioblastomů patří mutace a delece nádorových supresorů PTEN, p53 a amplifikace receptorů pro epidermální růstový faktor (EGFR) a trombocytární růstový faktor (PDGFR). Cílem projektu je 1) ověření vlivu PTEN na inhibici proliferace gliálních buněčných linií, 2) analýza vlivu PTEN na expresi vybraných proteinů regulujících dráhu PI3-K/PKB/Akt, MAPK, buněčný cyklus a regulátor angiogeneze trombospondin 1. 3) analýza vztahu mezi expresí PTEN a proteinůregulujících PI3-K/PKB/Akt, MAPK dráhu, buněčný cyklus a trombospondin 1 u souboru bioptických vzorků pacientů s low grade a high grade astrogliálními nádory. Pro experimenty plánujeme použít metody kultivace buněčných linií, transfekce DNA, detekce buněčné proliferace, elektroforézu proteinů, "Western blot" analýzu, imunocytochemickou a imunohistochemickou detekci.

• MeSH
• astrocytom genetika   MeSH
• fosfatidylinositol-3-kinasy MeSH
• glioblastom genetika   MeSH
• mitogenem aktivované proteinkinasy kinas MeSH
• nádorové supresorové proteiny MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biologie
• neurologie
• onkologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR