{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:44:27Z","timestamp":1783608267621,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:00:00Z","timestamp":1700524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Magyar Tudom\u00e1nyos Akad\u00e9mia","doi-asserted-by":"publisher","award":["BO\/00125\/22"],"award-info":[{"award-number":["BO\/00125\/22"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>TP53<\/jats:italic> aberrations predict chemoresistance and represent a contraindication for the use of standard chemoimmunotherapy in chronic lymphocytic leukaemia (CLL). Recent next\u2010generation sequencing (NGS)\u2010based studies have identified frequent low\u2010burden <jats:italic>TP53<\/jats:italic> mutations with variant allele frequencies below 10%, but the clinical impact of these low\u2010burden <jats:italic>TP53<\/jats:italic> mutations is still a matter of debate. In this study, we aimed to scrutinise the subclonal architecture and clinical impact of <jats:italic>TP53<\/jats:italic> mutations using a sensitive, NGS\u2010based mutation analysis in a \u2018real\u2010world\u2019 cohort of 901 patients with CLL. In total, 225 <jats:italic>TP53<\/jats:italic> mutations were identified in 17.5% (158\/901) of the patients; 48% of these alterations represented high\u2010burden mutations, while 52% were low\u2010burden <jats:italic>TP53<\/jats:italic> mutations. Low\u2010burden 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\u2010burden <jats:italic>TP53<\/jats:italic> mutation. Patients harbouring low\u2010burden <jats:italic>TP53<\/jats:italic> mutations had significantly lower time to first treatment compared to patients with wild\u2010type <jats:italic>TP53<\/jats:italic>. Our study has expanded the knowledge on the frequency, clonal architecture, and clinical impact of low\u2010burden <jats:italic>TP53<\/jats:italic> mutations. By demonstrating that patients with sole low\u2010burden <jats:italic>TP53<\/jats:italic> variants represent more than one\u2010third of patients with <jats:italic>TP53<\/jats:italic> mutations and have an increased risk for treatment initiation, our findings strengthen the need to redefine the threshold of <jats:italic>TP53<\/jats:italic> variant reporting to below 10% in the routine diagnostic setting.<\/jats:p>","DOI":"10.1002\/cjp2.351","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T13:54:57Z","timestamp":1700661297000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Low\u2010burden <scp><i>TP53<\/i><\/scp> mutations represent frequent genetic events in <scp>CLL<\/scp> with an increased risk for treatment 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