A comprehensive analysis of germline predisposition to early-onset ovarian cancer

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F24%3A00079891" target="_blank" >RIV/00209805:_____/24:00079891 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10482989 RIV/00216208:11310/24:10482989 RIV/00064211:_____/24:W0000004 RIV/00064165:_____/24:10482989

Výsledek na webu

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246516/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246516/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-024-66324-2" target="_blank" >10.1038/s41598-024-66324-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A comprehensive analysis of germline predisposition to early-onset ovarian cancer

Popis výsledku v původním jazyce

The subset of ovarian cancer (OC) diagnosed LESS-THAN OR EQUAL TO 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 x 10(-4)), and the presumably BC-specific PRS(313), which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 x 10(-4)) and diminished HLA diversity compared with controls(p = 3 x 10(-7)). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 x 10(-4)). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

Název v anglickém jazyce

A comprehensive analysis of germline predisposition to early-onset ovarian cancer

Popis výsledku anglicky

The subset of ovarian cancer (OC) diagnosed LESS-THAN OR EQUAL TO 30yo represents a distinct subgroup exhibiting disparities from late-onset OC in many aspects, including indefinite germline cancer predisposition. We performed DNA/RNA-WES with HLA-typing, PRS assessment and survival analysis in 123 early-onset OC-patients compared to histology/stage-matched late-onset and unselected OC-patients, and population-matched controls. Only 6/123(4.9%) early-onset OC-patients carried a germline pathogenic variant (GPV) in high-penetrance OC-predisposition genes. Nevertheless, our comprehensive germline analysis of early-onset OC-patients revealed two divergent trajectories of potential germline susceptibility. Firstly, overrepresentation analysis highlighted a connection to breast cancer (BC) that was supported by the CHEK2 GPV enrichment in early-onset OC(p = 1.2 x 10(-4)), and the presumably BC-specific PRS(313), which successfully stratified early-onset OC-patients from controls(p = 0.03). The second avenue pointed towards the impaired immune response, indicated by LY75-CD302 GPV(p = 8.3 x 10(-4)) and diminished HLA diversity compared with controls(p = 3 x 10(-7)). Furthermore, we found a significantly higher overall GPV burden in early-onset OC-patients compared to controls(p = 3.8 x 10(-4)). The genetic predisposition to early-onset OC appears to be a heterogeneous and complex process that goes beyond the traditional Mendelian monogenic understanding of hereditary cancer predisposition, with a significant role of the immune system. We speculate that rather a cumulative overall GPV burden than specific GPV may potentially increase OC risk, concomitantly with reduced HLA diversity.

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)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

2045-2322

Svazek periodika

14

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

16183

Kód UT WoS článku

001272466300041

EID výsledku v databázi Scopus

2-s2.0-85198400610