Rare deleterious germline variants and risk of lung cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F21%3A10424843" target="_blank" >RIV/00216208:11130/21:10424843 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15120/21:73609110
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CJF.0WbYOq" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CJF.0WbYOq</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41698-021-00146-7" target="_blank" >10.1038/s41698-021-00146-7</a>
Alternative languages
Result language
angličtina
Original language name
Rare deleterious germline variants and risk of lung cancer
Original language description
Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04-75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71-8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3' UTR (OR 4.33, 95%CI 2.03-9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73-11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33-5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.
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
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
npj Precision Oncology [online]
ISSN
2397-768X
e-ISSN
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Volume of the periodical
5
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
12
UT code for WoS article
000618865900001
EID of the result in the Scopus database
2-s2.0-85110190489