{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:50:43Z","timestamp":1789595443737,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012100","name":"Associazione Italiana Contro le Leucemie-Linfomi e Mieloma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012100","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chronic lymphocytic leukemia (CLL) is a hematological disorder with complex clinical and biological behavior.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutational status and cytogenetic assessment of the deletion of the corresponding locus (17p13.1) are considered the most relevant biomarkers associated with pharmaco\u2010predictive response, chemo\u2010refractoriness, and worse prognosis in CLL patients. The implementation of Next Generation Sequencing (NGS) methodologies in the clinical laboratory allows for comprehensively analyzing the\n                    <jats:italic>TP53<\/jats:italic>\n                    gene and detecting mutations with allele frequencies \u226410%, that is, \u201csubclonal mutations\u201d. We retrospectively studied\n                    <jats:italic>TP53<\/jats:italic>\n                    gene mutational status by NGS in 220 samples from 171 CLL patients.\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations were found in 60\/220 (27.3%) samples and 47\/171 (27.5%) patients. Interestingly, subclonal mutations could be detected in 31\/60 samples (51.7%) corresponding to 25 patients (25\/47, 53.2%). We identified 44 distinct subclonal\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations clustered in the central DNA\u2010binding domain of p53 protein (exons 5\u20138, codons 133\u2013286). Missense mutations were predominant (&gt;80%), whereas indels, nonsense, and splice site variants were less represented. All subclonal\n                    <jats:italic>TP53<\/jats:italic>\n                    variants but one [p.(Pro191fs)] were already described in NCI and\/or Seshat databases as \u201cdamaging\u201d and\/or \u201cprobably damaging\u201d mutations (38\/44, 86% and 6\/44, 14%, respectively). Longitudinal samples were available for 37 patients. Almost half of them displayed at least one\n                    <jats:italic>TP53<\/jats:italic>\n                    mutant subclone, which could be alone (4\/16, 25%) or concomitant with other\n                    <jats:italic>TP53<\/jats:italic>\n                    mutant clonal ones (12\/16, 75%); different patterns of mutational dynamics overtimes were documented. In conclusion, utilization of NGS in our \u201creal\u2010life\u201d cohort of CLL patients demonstrated an elevated frequency of subclonal\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations. This finding indicates the need for precisely identifying these mutations during disease since the clones carrying them may become predominant and be responsible for therapy failures.\n                  <\/jats:p>","DOI":"10.1002\/hon.3063","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T21:53:17Z","timestamp":1660341197000},"page":"962-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The spectrum of subclonal\n                    <i>TP53<\/i>\n                    mutations in chronic lymphocytic leukemia: A next generation sequencing retrospective study"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-1309","authenticated-orcid":false,"given":"Giuseppa","family":"De Luca","sequence":"first","affiliation":[{"name":"Molecular Diagnostic Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giannamaria","family":"Cerruti","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Lastraioli","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"Conte","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adalberto","family":"Ibatici","sequence":"additional","affiliation":[{"name":"Hematology Unit and Bone Marrow Transplantation IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikki","family":"Di Felice","sequence":"additional","affiliation":[{"name":"Hematology Unit and Bone Marrow Transplantation IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fortunato","family":"Morabito","sequence":"additional","affiliation":[{"name":"Biotechnology Research Unit Aprigliano A.O.\/ASP of Cosenza  Cosenza Italy"},{"name":"Department of Hematology and Bone Marrow Transplant Unit Augusta Victoria Hospital  East Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-4998","authenticated-orcid":false,"given":"Paola","family":"Monti","sequence":"additional","affiliation":[{"name":"Mutagenesis and Cancer Prevention Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Fronza","sequence":"additional","affiliation":[{"name":"Mutagenesis and Cancer Prevention Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Matis","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Colombo","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Fabris","sequence":"additional","affiliation":[{"name":"Hematology Unit Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Ciarrocchi","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Research Azienda USL\u2010IRCCS di Reggio Emilia  Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Neri","sequence":"additional","affiliation":[{"name":"Scientific Directorate Azienda USL\u2010IRCCS di Reggio Emilia  Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Menichini","sequence":"additional","affiliation":[{"name":"Mutagenesis and Cancer Prevention Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manlio","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nozza","sequence":"additional","affiliation":[{"name":"Department of Pathology IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6643-7083","authenticated-orcid":false,"given":"Franco","family":"Fais","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"},{"name":"Department of Experimental Medicine University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-1101","authenticated-orcid":false,"given":"Giovanna","family":"Cutrona","sequence":"additional","affiliation":[{"name":"Molecular Pathology Unit IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariella","family":"Dono","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Unit IRCCS Ospedale Policlinico San Martino  Genoa 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