Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F25%3A00081493" target="_blank" >RIV/65269705:_____/25:00081493 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/25:00140947
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1002/hem3.70065" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/hem3.70065</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/hem3.70065" target="_blank" >10.1002/hem3.70065</a>
Alternative languages
Result language
angličtina
Original language name
Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL
Original language description
In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect TP53 variants LESS-THAN OR EQUAL TO10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.6%, 94.5%, and 94.8% at 1%, 2%, and 3% VAF cut-off, respectively. While only one false positive (FP) result was reported at >2% VAF, it was more challenging to distinguish true variants <2% VAF from background noise (37 FPs reported by 9 laboratories). The impact of low-VAF variants on time-to-second-treatment (TTST) and overall survival (OS) was investigated in a series of 1092 patients. Among patients not treated with targeted agents, patients with low-VAF TP53 variants had shorter TTST and OS versus wt-TP53 patients, and the relative risk of second-line treatment or death increased continuously with increasing VAF. Targeted therapy in GREATER-THAN OR EQUAL TO2 line diminished the difference in OS between patients with low-VAF TP53 variants and wt-TP53 patients, while patients with high-VAF TP53 variants had inferior OS compared to wild type-TP53 cases. Altogether, NGS-based approaches are technically capable of detecting low-VAF variants. No strict threshold can be suggested from a technical standpoint, laboratories reporting TP53 mutations should participate in a standardized validation set-up. Finally, whereas low-VAF variants affected outcomes in patients receiving chemoimmunotherapy, their impact on those treated with novel therapies remains undetermined. Our results pave the way for the harmonized and accurate TP53 assessment, which is indispensable for elucidating the role of TP53 mutations in targeted treatment.
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
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
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
HemaSphere
ISSN
2572-9241
e-ISSN
2572-9241
Volume of the periodical
9
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
13
Pages from-to
"e70065"
UT code for WoS article
001412437600001
EID of the result in the Scopus database
2-s2.0-85215519292