Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation

László, Tamás and Kotmayer, Lili and Fésüs, Viktória and Hegyi, Lajos and Gróf, Stefánia and Nagy, Ákos and Kajtár, Béla and Balogh, Alexandra and Weisinger, Júlia and Masszi, Tamás and Nagy, Zsolt and Farkas, Péter and Demeter, Judit and Istenes, Ildikó and Szász, Róbert and Gergely, Lajos and Sulák, Adrienn and Borbényi, Zita and Lévai, Dóra and Schneider, Tamás and Pettendi, Piroska and Bódai, Emese and Szerafin, László and Rejtő, László and Bátai, Árpád and Dömötör, Mária and Sánta, Hermina and Plander, Márk and Szendrei, Tamás and Hamed, Aryan and Lázár, Zsolt and Pauker, Zsolt and Radványi, Gáspár and Kiss, Adrienn and Körösmezey, Gábor and Jakucs, János and Dombi, Péter and Simon, Zsófia and Klucsik, Zsolt and Gurzó, Mihály and Tiboly, Márta and Vidra, Tímea and Ilonczai, Péter and Bors, András and Andrikovics, Hajnalka and Egyed, Miklós and Székely, Tamás and Masszi, András and Alpár, Donát and Matolcsy, András and Bödör, Csaba (2024) Low-burden TP53 mutations represent frequent genetic events in CLL with an increased risk for treatment initiation. The Journal of Pathology: Clinical Research.

Preview

Text The Journal of Pathology CR - 2023 - László - Low‐burden TP53 mutations represent frequent genetic events in CLL with an.pdf Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB) | Preview

Abstract

TP53 aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next-generation sequencing (NGS)-based studies have identified frequent low-burden TP53 mutations with variant allele frequencies below 10%, but the clinical impact of these low-burden TP53 mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of TP53 mutations using a sensitive, NGS-based mutation analysis in a ‘real-world’ cohort of 901 patients with CLL. In total, 225 TP53 mutations were identified in 17.5% (158/901) of the patients; 48% of these alterations represented high-burden mutations, while 52% were low-burden TP53 mutations. Low-burden mutations as sole alterations were identified in 39% (62/158) of all mutated cases with 82% (51/62) of these being represented by a single low-burden TP53 mutation. Patients harbouring low-burden TP53 mutations had significantly lower time to first treatment compared to patients with wild-type TP53. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low-burden TP53 mutations. By demonstrating that patients with sole low-burden TP53 variants represent more than one-third of patients with TP53 mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of TP53 variant reporting to below 10% in the routine diagnostic setting.

Actions (login required)

Edit Item