Identification of a novel RSPO1-NUMT insertion in a LUAD patient cohort and the challenges and insights into NUMT detection highlighting the importance of reference genomes and population databases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F27661989%3A_____%2F25%3A10002837" target="_blank" >RIV/27661989:_____/25:10002837 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10505169 RIV/00216208:11120/25:43929025 RIV/00216208:11320/25:10505169 RIV/00064190:_____/25:10001417 RIV/00064165:_____/25:10505169

Výsledek na webu

<a href="http://:https://tlcr.amegroups.org/article/view/107285/html" target="_blank" >http://:https://tlcr.amegroups.org/article/view/107285/html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.21037/tlcr-2025-586" target="_blank" >10.21037/tlcr-2025-586</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of a novel RSPO1-NUMT insertion in a LUAD patient cohort and the challenges and insights into NUMT detection highlighting the importance of reference genomes and population databases

Popis výsledku v původním jazyce

Nuclear mitochondrial DNA sequences (NUMTs) represent mitochondrial DNA fragments integrated into the nuclear genome with potential clinical significance particularly in the pathology of cancer which have be identified in recent whole-genome sequencing (WGS) studies. Combining NUMT in silico analysis on WGS from The Cancer Genome Atlas with further characterize with molecular-genomic experiments (PCR assay and sequencing) across lung adenocarcinoma (LUAD) patient cohort tumor samples and incorporating important clinical parameters. Our molecular analysis of 298 LUAD samples revealed a RSPO1 gene NUMT insertion in approximately 31% of cases (29% heterozygous, 2% homozygous). This RSPO1-NUMT insertion&apos;s presence was observed across matched blood, healthy lung, and tumor samples confirming its germline origin. Notably, homozygous carriers exhibited significantly earlier disease onset (mean age: 54 vs. 63.3 years; P=0.04) and a trend toward advanced-stage disease at diagnosis compared to no NUMT-insertion or heterozygous individuals. We report a novel NUMT insertion of the RSPO1 gene, which is a key regulator in the oncogenic WNT signaling pathway. Our findings also highlight technical challenges in NUMT detection across genome builds and databases, with significant discrepancies observed between reference genomes and population frequency estimates. We propose that this homozygous RSPO1-NUMT insertion may represent a previously unrecognized predisposing factor for LUAD development and progression through modulation of RSPO1 expression and subsequent WNT pathway activation, potentially influencing tumor vascularization, drug response, and disease progression.

Název v anglickém jazyce

Identification of a novel RSPO1-NUMT insertion in a LUAD patient cohort and the challenges and insights into NUMT detection highlighting the importance of reference genomes and population databases

Popis výsledku anglicky

Nuclear mitochondrial DNA sequences (NUMTs) represent mitochondrial DNA fragments integrated into the nuclear genome with potential clinical significance particularly in the pathology of cancer which have be identified in recent whole-genome sequencing (WGS) studies. Combining NUMT in silico analysis on WGS from The Cancer Genome Atlas with further characterize with molecular-genomic experiments (PCR assay and sequencing) across lung adenocarcinoma (LUAD) patient cohort tumor samples and incorporating important clinical parameters. Our molecular analysis of 298 LUAD samples revealed a RSPO1 gene NUMT insertion in approximately 31% of cases (29% heterozygous, 2% homozygous). This RSPO1-NUMT insertion&apos;s presence was observed across matched blood, healthy lung, and tumor samples confirming its germline origin. Notably, homozygous carriers exhibited significantly earlier disease onset (mean age: 54 vs. 63.3 years; P=0.04) and a trend toward advanced-stage disease at diagnosis compared to no NUMT-insertion or heterozygous individuals. We report a novel NUMT insertion of the RSPO1 gene, which is a key regulator in the oncogenic WNT signaling pathway. Our findings also highlight technical challenges in NUMT detection across genome builds and databases, with significant discrepancies observed between reference genomes and population frequency estimates. We propose that this homozygous RSPO1-NUMT insertion may represent a previously unrecognized predisposing factor for LUAD development and progression through modulation of RSPO1 expression and subsequent WNT pathway activation, potentially influencing tumor vascularization, drug response, and disease progression.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Translational Lung Cancer Research

ISSN

2218-6751

e-ISSN

2226-4477

Svazek periodika

14

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

CN - Čínská lidová republika

Počet stran výsledku

11

Strana od-do

4560-4570

Kód UT WoS článku

001622655300029

EID výsledku v databázi Scopus

2-s2.0-105020433601