J 2025

Detection of clinically relevant variants in the TP53 gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL

PAVLOVÁ, Šárka, Jitka MALČÍKOVÁ, Lenka RADOVÁ, Silvia BONFIGLIO, Jack B COWLAND et. al.

Basic information

Original 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

Authors

PAVLOVÁ, Šárka, Jitka MALČÍKOVÁ, Lenka RADOVÁ, Silvia BONFIGLIO, Jack B COWLAND, Christian BRIEGHEL, Mette K ANDERSEN, Maria KARYPIDOU, Bella BIDERMAN, Michael DOUBEK, Gregory LAZARIAN, Inmaculada RAPADO, Matthijs VYNCK, Naomi A PORRET, Martin ANDRES, Dina ROSENBERG, Dvora SAHAR, Carolina MARTINEZ-LAPERCHE, Ismael BUNO, Andrew HINDLEY, David DONALDSON, Julio B SANCHEZ, Jose A GARCIA-MARCO, Alicia SERRANO-ALCALA, Blanca FERRER-LORES, Concepcion FERNANDEZ-RODRIGUEZ, Beatriz BELLOSILLO, Stephan STILGENBAUER, Eugen TAUSCH, Hero NIKDIN, Fiona QUINN, Emer ATKINSON, van de Corput LISETTE, Cafer YILDIZ, Cristina BILBAO-SIEYRO, Yanira FLORIDO, Christian THIEDE, Caroline SCHUSTER, Anastazja STOJ, Sylwia CZEKALSKA, Anastasia CHATZIDIMITRIOU, Stamatia LAIDOU, Audrey BIDET, Charles DUSSIAU, Friedel NOLLET, Giovanna PIRAS, Maria MONNE, Svetlana SMIRNOVA, Eugene NIKITIN, Ivan SLOMA, Alexis CLAUDEL, Laetitia LARGEAUD, Loic YSEBAERT, Peter J M VALK, Amy CHRISTIAN, Renata WALEWSKA, David OSCIER, Marta SEBASTIAO, da Silva Maria GOMES, Piero GALIENI, Mario ANGELINI, Davide ROSSI, Valeria SPINA, Sonia MATOS, Vania MARTINS, Tomasz STOKLOSA, Monika PEPEK, Panagiotis BALIAKAS, Rafa ANDREU, Irene LUNA, Tiina KAHRE, Ulle MURUMETS, Tereza PIKOUSOVA, Terezia KURUCOVA, Sophie LAIRD, Daniel WARD, Miguel ALCOCEBA, Ana BALANZATEGUI, Lydia SCARFO, Francesca GANDINI, Ettore ZAPPAROLI, Adoracion BLANCO, Pau ABRISQUETA, Ana E RODRIGUEZ-VICENTE, Rocio BENITO, Clotilde BRAVETTI, Frederic DAVI, Paula GAMEIRO, Joaquin MARTINEZ-LOPEZ, Barbara TAZON-VEGA, Fanny BARAN-MARSZAK, Zadie DAVIS, Mark CATHERWOOD, Andrey SUDARIKOV, Richard ROSENQUIST, Carsten U NIEMANN, Kostas STAMATOPOULOS, Paolo GHIA and Šárka POSPÍŠILOVÁ

Edition

HemaSphere, Philadelphia, Wilkins, 2025, 2572-9241

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Lékařská fakulta – Repository – Repository

DOI

http://dx.doi.org/10.1002/hem3.70065

UT WoS

001412437600001

Keywords in English

chronic lymphocytic leukemia; next-generation sequencing; TP53 variants

Links

LM2023067, research and development project. LX22NPO5102, research and development project. NW24-03-00114, research and development project.
Changed: 4/4/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

lt;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 ≥2 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.
Displayed: 30/4/2025 08:46