Informace o publikaci

A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations

Autoři	STRUZINSKA Ivana HAJKOVA Nikola HOJNY Jan KRKAVCOVA Eva MICHALKOVA Romana DVORAK Jiri NEMEJCOVA Kristyna MATEJ Radoslav LACO Jan DROZENOVA Jana FABIAN Pavel HAUSNEROVÁ Jitka MEHES Gabor SKAPA Petr SVAJDLER Marian CIBULA David FRUHAUF Filip KENDALL BARTU Michaela Kendall DUNDR Pavel
Rok publikování	2023
Druh	Článek v odborném periodiku
Časopis / Zdroj	Diagnostic Pathology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
www	https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01358-0
Doi	http://dx.doi.org/10.1186/s13000-023-01358-0
Klíčová slova	Capture DNA NGS; RNA-Seq; Rare ovarian tumors; POLE mutation
Popis	BackgroundMolecular 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.Methods113 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.ResultsThe 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.ConclusionsThe 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.