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Open Access 01-12-2023 | Research

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

Authors: Ivana Stružinská, Nikola Hájková, Jan Hojný, Eva Krkavcová, Romana Michálková, Jiří Dvořák, Kristýna Němejcová, Radoslav Matěj, Jan Laco, Jana Drozenová, Pavel Fabian, Jitka Hausnerová, Gábor Méhes, Petr Škapa, Marián Švajdler, David Cibula, Filip Frühauf, Michaela Kendall Bártů, Pavel Dundr

Published in: Diagnostic Pathology | Issue 1/2023

Abstract

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 POLE^mut 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 POLE^mut 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.

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Title: A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations
Authors: Ivana Stružinská
Nikola Hájková
Jan Hojný
Eva Krkavcová
Romana Michálková
Jiří Dvořák
Kristýna Němejcová
Radoslav Matěj
Jan Laco
Jana Drozenová
Pavel Fabian
Jitka Hausnerová
Gábor Méhes
Petr Škapa
Marián Švajdler
David Cibula
Filip Frühauf
Michaela Kendall Bártů
Pavel Dundr
Publication date: 01-12-2023
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2023
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-023-01358-0

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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