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
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11110/25:10505169 RIV/00216208:11120/25:43929025 RIV/00216208:11320/25:10505169 RIV/00064190:_____/25:10001417 RIV/00064165:_____/25:10505169
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
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
Original language description
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'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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Translational Lung Cancer Research
ISSN
2218-6751
e-ISSN
2226-4477
Volume of the periodical
14
Issue of the periodical within the volume
10
Country of publishing house
CN - CHINA
Number of pages
11
Pages from-to
4560-4570
UT code for WoS article
001622655300029
EID of the result in the Scopus database
2-s2.0-105020433601