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

J 2023

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

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA et. al.

Základní údaje

Originální název

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

Autoři

STRUZINSKA, Ivana (203 Česká republika, garant), Nikola HAJKOVA (203 Česká republika), Jan HOJNY (203 Česká republika), Eva KRKAVCOVA (203 Česká republika), Romana MICHALKOVA (203 Česká republika), Jiri DVORAK (203 Česká republika), Kristyna NEMEJCOVA (203 Česká republika), Radoslav MATEJ (203 Česká republika), Jan LACO (203 Česká republika), Jana DROZENOVA (203 Česká republika), Pavel FABIAN (203 Česká republika), Jitka HAUSNEROVÁ (203 Česká republika, domácí), Gabor MEHES (203 Česká republika), Petr SKAPA (203 Česká republika), Marian SVAJDLER (203 Česká republika), David CIBULA (203 Česká republika), Filip FRUHAUF (203 Česká republika), Michaela Kendall KENDALL BARTU (203 Česká republika) a Pavel DUNDR (203 Česká republika)

Vydání

Diagnostic Pathology, LONDON, BMC, 2023, 1746-1596

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30109 Pathology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.600 v roce 2022

Kód RIV

RIV/00216224:14110/23:00131201

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1186/s13000-023-01358-0

UT WoS

001002555100001

Klíčová slova anglicky

Capture DNA NGS; RNA-Seq; Rare ovarian tumors; POLE mutation

Štítky

14110230, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 1. 2024 13:29, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

90233, velká výzkumná infrastruktura

Název: BBMRI.cz IV

Citovat

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA, Jiri DVORAK, Kristyna NEMEJCOVA, Radoslav MATEJ, Jan LACO, Jana DROZENOVA, Pavel FABIAN, Jitka HAUSNEROVÁ, Gabor MEHES, Petr SKAPA, Marian SVAJDLER, David CIBULA, Filip FRUHAUF, Michaela Kendall KENDALL BARTU a Pavel DUNDR. A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations. Diagnostic Pathology. LONDON: BMC, 2023, roč. 18, č. 1, s. 1-12. ISSN 1746-1596. Dostupné z: https://dx.doi.org/10.1186/s13000-023-01358-0.

@article{2296992,
   author = {Struzinska, Ivana and Hajkova, Nikola and Hojny, Jan and Krkavcova, Eva and Michalkova, Romana and Dvorak, Jiri and Nemejcova, Kristyna and Matej, Radoslav and Laco, Jan and Drozenova, Jana and Fabian, Pavel and Hausnerová, Jitka and Mehes, Gabor and Skapa, Petr and Svajdler, Marian and Cibula, David and Fruhauf, Filip and Kendall Bartu, Michaela Kendall and Dundr, Pavel},
   article_location = {LONDON},
   article_number = {1},
   doi = {http://dx.doi.org/10.1186/s13000-023-01358-0},
   keywords = {Capture DNA NGS; RNA-Seq; Rare ovarian tumors; POLE mutation},
   language = {eng},
   issn = {1746-1596},
   journal = {Diagnostic Pathology},
   title = {A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations},
   url = {https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01358-0},
   volume = {18},
   year = {2023}
}

TY  - JOUR
ID  - 2296992
AU  - 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
PY  - 2023
TI  - A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations
JF  - Diagnostic Pathology
VL  - 18
IS  - 1
SP  - 1-12
EP  - 1-12
PB  - BMC
SN  - 17461596
KW  - Capture DNA NGS
KW  - RNA-Seq
KW  - Rare ovarian tumors
KW  - POLE mutation
UR  - https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-023-01358-0
N2  - 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.
ER  -

STRUZINSKA, Ivana, Nikola HAJKOVA, Jan HOJNY, Eva KRKAVCOVA, Romana MICHALKOVA, Jiri DVORAK, Kristyna NEMEJCOVA, Radoslav MATEJ, Jan LACO, Jana DROZENOVA, Pavel FABIAN, Jitka HAUSNEROVÁ, Gabor MEHES, Petr SKAPA, Marian SVAJDLER, David CIBULA, Filip FRUHAUF, Michaela Kendall KENDALL BARTU a Pavel DUNDR. A comprehensive molecular analysis of 113 primary ovarian clear cell carcinomas reveals common therapeutically significant aberrations. \textit{Diagnostic Pathology}. LONDON: BMC, 2023, roč.~18, č.~1, s.~1-12. ISSN~1746-1596. Dostupné z: https://dx.doi.org/10.1186/s13000-023-01358-0.

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