{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:31:25Z","timestamp":1775932285228,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["17SGR437"],"award-info":[{"award-number":["17SGR437"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de 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III\/FEDER","award":["17SGR437"],"award-info":[{"award-number":["17SGR437"]}]},{"name":"Instituto de Salud Carlos III\/FEDER","award":["GLD17\/00282"],"award-info":[{"award-number":["GLD17\/00282"]}]},{"name":"Instituto de Salud Carlos III\/FEDER","award":["FPU17\/00361"],"award-info":[{"award-number":["FPU17\/00361"]}]},{"name":"Instituto de Salud Carlos III\/FEDER","award":["FEHH-Janssen"],"award-info":[{"award-number":["FEHH-Janssen"]}]},{"name":"Instituto de Salud Carlos III\/FEDER","award":["PT17\/0015\/0011"],"award-info":[{"award-number":["PT17\/0015\/0011"]}]},{"name":"Xarxa de Bancs de tumors\/Pla Director d\u2019Oncologia de Catalunya (XBTC)","award":["17SGR437"],"award-info":[{"award-number":["17SGR437"]}]},{"name":"Xarxa de Bancs de tumors\/Pla Director d\u2019Oncologia de Catalunya (XBTC)","award":["GLD17\/00282"],"award-info":[{"award-number":["GLD17\/00282"]}]},{"name":"Xarxa de Bancs de tumors\/Pla Director d\u2019Oncologia de Catalunya (XBTC)","award":["FPU17\/00361"],"award-info":[{"award-number":["FPU17\/00361"]}]},{"name":"Xarxa de Bancs de tumors\/Pla Director d\u2019Oncologia de Catalunya (XBTC)","award":["FEHH-Janssen"],"award-info":[{"award-number":["FEHH-Janssen"]}]},{"name":"Xarxa de Bancs de tumors\/Pla Director d\u2019Oncologia de Catalunya (XBTC)","award":["PT17\/0015\/0011"],"award-info":[{"award-number":["PT17\/0015\/0011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3\u201326). Two patterns were identified: one with rearrangements clustered in the region with cth (3\/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6\/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; p = 0.013). However, when stratifying patients based on TP53 status, cth did not affect TTFT. Only TP53 maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; p = 0.029). Our findings suggest that TP53 abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset.<\/jats:p>","DOI":"10.3390\/cancers14153715","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"3715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9175-7102","authenticated-orcid":false,"given":"Silvia","family":"Ramos-Campoy","sequence":"first","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9627-4978","authenticated-orcid":false,"given":"Anna","family":"Puiggros","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Kamaso","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00edlvia","family":"Be\u00e0","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Pathology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Bougeon","sequence":"additional","affiliation":[{"name":"Oncogenomic Laboratory, Hematology Service, Lausanne University Hospital, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Larr\u00e1yoz","sequence":"additional","affiliation":[{"name":"Cytogenetics and Hematological Genetics Services, Department of Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolors","family":"Costa","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Pathology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Parker","sequence":"additional","affiliation":[{"name":"Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8370-5190","authenticated-orcid":false,"given":"Gian Matteo","family":"Rigolin","sequence":"additional","affiliation":[{"name":"Hematology Section, St. Anna University Hospital, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Laura","family":"Blanco","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital de la Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-6192","authenticated-orcid":false,"given":"Rosa","family":"Collado","sequence":"additional","affiliation":[{"name":"Department of Hematology, Consorcio Hospital General Universitario, 46014 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Idoya","family":"Anc\u00edn","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemotherapy, Hospital Universitario Cruces, 48903 Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Salgado","sequence":"additional","affiliation":[{"name":"Cytogenetics Laboratory, Hematology Department, Fundaci\u00f3n Jim\u00e9nez D\u00edaz, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco A.","family":"Moro-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tycho","family":"Baumann","sequence":"additional","affiliation":[{"name":"Hematopathology Section, Department of Pathology, Hospital Cl\u00ednic, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-6189","authenticated-orcid":false,"given":"Eva","family":"Gimeno","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Applied Clinical Research in Hematological Malignances, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital de la Santa Creu I Sant Pau, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Salido","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-9130","authenticated-orcid":false,"given":"Xavier","family":"Calvo","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-3008","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9","family":"Calasanz","sequence":"additional","affiliation":[{"name":"Cytogenetics and Hematological Genetics Services, Department of Genetics, University of Navarra, 31008 Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Cuneo","sequence":"additional","affiliation":[{"name":"Hematology Section, St. Anna University Hospital, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-6668","authenticated-orcid":false,"given":"Florence","family":"Nguyen-Khac","sequence":"additional","affiliation":[{"name":"Sorbonne University, Hematology Department, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, APHP, INSERM U1138, 75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Oscier","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth BH7 7DW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Haferlach","sequence":"additional","affiliation":[{"name":"MLL Munich Leukemia Laboratory, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-2881","authenticated-orcid":false,"given":"Jonathan C.","family":"Strefford","sequence":"additional","affiliation":[{"name":"Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline","family":"Schoumans","sequence":"additional","affiliation":[{"name":"Oncogenomic Laboratory, Hematology Service, Lausanne University Hospital, 1011 Lausanne, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4294-8145","authenticated-orcid":false,"given":"Blanca","family":"Espinet","sequence":"additional","affiliation":[{"name":"Molecular Cytogenetics and Hematological Cytology Laboratories, Pathology Department, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Translational Research on Hematological Neoplasms Group, Cancer Research Program, Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1182\/blood-2016-01-691550","article-title":"Complex karyotypes and KRAS and POT1 mutations impact outcome in CLL after chlorambucil-based chemotherapy or chemoimmunotherapy","volume":"128","author":"Herling","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54297","DOI":"10.18632\/oncotarget.17350","article-title":"Patients with chronic lymphocytic leukemia and complex karyotype show an adverse outcome even in absence of TP53\/ATM FISH deletions","volume":"8","author":"Puiggros","year":"2017","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1182\/blood-2017-03-772285","article-title":"In CLL, comorbidities and the complex karyotype are associated with an inferior outcome independently of CLL-IPI","volume":"129","author":"Rigolin","year":"2017","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1182\/blood-2018-09-873083","article-title":"Cytogenetic complexity in chronic lymphocytic leukemia: Definitions, associations, and clinical impact","volume":"133","author":"Baliakas","year":"2019","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3612","DOI":"10.1002\/cncr.29566","article-title":"Complex karyotype is a stronger predictor than del(17p) for an inferior outcome in relapsed or refractory chronic lymphocytic leukemia patients treated with ibrutinib-based regimens","volume":"121","author":"Thompson","year":"2015","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1509981","article-title":"Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia","volume":"374","author":"Byrd","year":"2016","journal-title":"N. 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Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S1470-2045(15)00465-9","article-title":"Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): A randomised, double-blind, phase 3 study","volume":"17","author":"Cramer","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1182\/blood-2017-01-763003","article-title":"Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax","volume":"129","author":"Anderson","year":"2017","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1182\/blood-2017-10-810044","article-title":"Single agent ibrutinib in treatment-na\u0131ve and relapsed\/refractory chronic lymphocytic leukemia: A 5-year experience","volume":"131","author":"Furman","year":"2018","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/leu.2017.175","article-title":"Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL\/SLL","volume":"32","author":"Brown","year":"2018","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.3324\/haematol.2018.193615","article-title":"Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States","volume":"103","author":"Mato","year":"2018","journal-title":"Haematologica"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1182\/blood.2019003451","article-title":"High efficacy of venetoclax plus obinutuzumab in patients with complex karyotype and chronic lymphocytic leukemia","volume":"135","author":"Lilienweiss","year":"2020","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1200\/JCO.20.00948","article-title":"Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations from the MURANO Phase III Study","volume":"38","author":"Kater","year":"2020","journal-title":"J. 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