Whole Exome Sequencing of Epithelial Ovarian Carcinomas Differing in Resistance to Platinum Therapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F22%3A10447719" target="_blank" >RIV/00216208:11140/22:10447719 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00669806:_____/22:10447719 RIV/00064173:_____/22:43924071 RIV/00064203:_____/22:10447719 RIV/75010330:_____/22:00014092 a 2 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Xlle92_HGG" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Xlle92_HGG</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.26508/lsa.202201551" target="_blank" >10.26508/lsa.202201551</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Whole Exome Sequencing of Epithelial Ovarian Carcinomas Differing in Resistance to Platinum Therapy

Popis výsledku v původním jazyce

Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in TP53 and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations in PABPC1, PABPC3, and TFAM co-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.

Název v anglickém jazyce

Whole Exome Sequencing of Epithelial Ovarian Carcinomas Differing in Resistance to Platinum Therapy

Popis výsledku anglicky

Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate in TP53 and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations in PABPC1, PABPC3, and TFAM co-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Life Science Alliance

ISSN

2575-1077

e-ISSN

2575-1077

Svazek periodika

5

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

e202201551

Kód UT WoS článku

000966879400001

EID výsledku v databázi Scopus

2-s2.0-85140143993