{"entity": "researcher", "timestamp": "2026-09-26T01:25:57.156Z", "family": "Gaidano", "given": "Gianluca", "initials": "G", "orcid": "0000-0002-4681-0151", "affiliations": ["Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c61a087170e49ae9f062617c751153e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c61a087170e49ae9f062617c751153e"}}, "publications": [{"entity": "publication", "iuid": "74729dc65e004ac79d33f36fce0ed5ba", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/74729dc65e004ac79d33f36fce0ed5ba.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/74729dc65e004ac79d33f36fce0ed5ba"}}, "title": "Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.", "authors": [{"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Shuai", "given": "Shimin", "initials": "S", "orcid": "0000-0002-9527-8018", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3896d0cb0c3b4d0fb8b34e39e654428c.json"}}, {"family": "Clot", "given": "Guillem", "initials": "G", "orcid": "0000-0003-2588-7413", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ff9667b5750841499b2cddfa2aba3294.json"}}, {"family": "Hilton", "given": "Laura K", "initials": "LK", "orcid": "0000-0002-6413-6586", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f06e235a0e1b40c68e292ef5420ed157.json"}}, {"family": "Diaz-Navarro", "given": "Ander", "initials": "A"}, {"family": "Mart\u00edn", "given": "Silvia", "initials": "S"}, {"family": "Royo", "given": "Romina", "initials": "R"}, {"family": "Baumann", "given": "Tycho", "initials": "T"}, {"family": "Kulis", "given": "Marta", "initials": "M"}, {"family": "L\u00f3pez-Oreja", "given": "Irene", "initials": "I"}, {"family": "Cossio", "given": "Manuel", "initials": "M"}, {"family": "Lu", "given": "Junyan", "initials": "J", "orcid": "0000-0002-9211-0746", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d6b5e8ff9f04ebc97f0086446bb2a95.json"}}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Young", "given": "Emma", "initials": "E"}, {"family": "Plevova", "given": "Karla", "initials": "K", "orcid": "0000-0002-6148-8877", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a4174bc21ce468a90d6f7cba6688179.json"}}, {"family": "Knisbacher", "given": "Binyamin A", "initials": "BA"}, {"family": "Lin", "given": "Ziao", "initials": "Z"}, {"family": "Hahn", "given": "Cynthia K", "initials": "CK"}, {"family": "Bousquets", "given": "Pablo", "initials": "P", "orcid": "0000-0002-2969-008X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7e649e6efb5b4b55b52b0846ca125be2.json"}}, {"family": "Alcoceba", "given": "Miguel", "initials": "M", "orcid": "0000-0002-3819-4846", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30856cb02a2f46e6a4a4ee435dd985ee.json"}}, {"family": "Gonz\u00e1lez", "given": "Marcos", "initials": "M"}, {"family": "Colado", "given": "Enrique", "initials": "E", "orcid": "0000-0001-8675-8207", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69bc9ef7e1db420ba922b82cc9992ae9.json"}}, {"family": "Payer", "given": "\u00c1ngel R", "initials": "\u00c1R"}, {"family": "Aymerich", "given": "Marta", "initials": "M"}, {"family": "Terol", "given": "Mar\u00eda J", "initials": "MJ"}, {"family": "Rivas-Delgado", "given": "Alfredo", "initials": "A"}, {"family": "Enjuanes", "given": "Anna", "initials": "A"}, {"family": "Ruiz-Gasp\u00e0", "given": "S\u00edlvia", "initials": "S"}, {"family": "Chatzikonstantinou", "given": "Thomas", "initials": "T", "orcid": "0000-0003-4105-1253", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a205228c1594457fbd55004721eb19c3.json"}}, {"family": "H\u00e4gerstrand", "given": "Daniel", "initials": "D", "orcid": "0000-0001-7270-0776", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c3221dc6f79b4d77bea303ab5e2b6fd2.json"}}, {"family": "Jylh\u00e4", "given": "Cecilia", "initials": "C"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Stranska", "given": "Kamila", "initials": "K", "orcid": "0000-0001-7678-1163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4e117c63824743888c475df6b819f05f.json"}}, {"family": "Doubek", "given": "Michael", "initials": "M", "orcid": "0000-0002-1269-6282", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69820fa805ac43ad892da50ac25d3e72.json"}}, {"family": "van Gastel-Mol", "given": "Ellen J", "initials": "EJ"}, {"family": "Davis", "given": "Zadie", "initials": "Z"}, {"family": "Walewska", "given": "Renata", "initials": "R"}, {"family": "Scarf\u00f2", "given": "Lydia", "initials": "L", "orcid": "0000-0002-0844-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7697d7b279ae48a387843c617f30fa3c.json"}}, {"family": "Trentin", "given": "Livio", "initials": "L", "orcid": "0000-0003-1222-6149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/820ab4c1a5534ada88d9c318fa8aa2e1.json"}}, {"family": "Visentin", "given": "Andrea", "initials": "A", "orcid": "0000-0003-0271-7200", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/10a25bb174034d55a6a2f0fccb036f02.json"}}, {"family": "Parikh", "given": "Sameer A", "initials": "SA", "orcid": "0000-0002-3221-7314", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a88ede10daa4046aa907682e1b8f8b8.json"}}, {"family": "Rabe", "given": "Kari G", "initials": "KG", "orcid": "0000-0002-7313-1875", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ffc22e22bdfd4d85bb699236989449cf.json"}}, {"family": "Moia", "given": "Riccardo", "initials": "R", "orcid": "0000-0001-7393-1138", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/35dc8f45c11b4d58999560cc83911a5e.json"}}, {"family": "Armand", "given": "Marine", "initials": "M", "orcid": "0000-0001-8906-3128", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4076e069779745059ba33556a6f4b295.json"}}, {"family": "Rossi", "given": "Davide", "initials": "D"}, {"family": "Davi", "given": "Frederic", "initials": "F"}, {"family": "Gaidano", "given": "Gianluca", "initials": "G", "orcid": "0000-0002-4681-0151", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c61a087170e49ae9f062617c751153e.json"}}, {"family": "Kay", "given": "Neil E", "initials": "NE", "orcid": "0000-0002-5951-5055", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8ed8e38f552b44c28e3a32023c07b537.json"}}, {"family": "Shanafelt", "given": "Tait D", "initials": "TD"}, {"family": "Ghia", "given": "Paolo", "initials": "P", "orcid": "0000-0003-3750-7342", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/475d35f1a3c446819b2f24be819c2dee.json"}}, {"family": "Oscier", "given": "David", "initials": "D"}, {"family": "Langerak", "given": "Anton W", "initials": "AW", "orcid": "0000-0002-2078-3220", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/535a658cf9db4176b46671be08e4f909.json"}}, {"family": "Be\u00e0", "given": "S\u00edlvia", "initials": "S", "orcid": "0000-0001-7192-2385", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/11db86f06c3340878b764b6d3ae9ecf0.json"}}, {"family": "L\u00f3pez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Neuberg", "given": "Donna", "initials": "D", "orcid": "0000-0003-2566-3145", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/70b2f9e23251469987cbe7b42d38dc58.json"}}, {"family": "Wu", "given": "Catherine J", "initials": "CJ", "orcid": "0000-0002-3348-5054", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d71b7e5cfa1c49d994df22a9a9657686.json"}}, {"family": "Getz", "given": "Gad", "initials": "G", "orcid": "0000-0002-0936-0753", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc65099492394065bb61f94c89425aa3.json"}}, {"family": "Pospisilova", "given": "Sarka", "initials": "S", "orcid": "0000-0001-7136-2680", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75467f2097fe4bcfb274e40e46cfbf12.json"}}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f6107d6f774ee6acb2c66ecfcb90cc.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc038c13a8cb44bd93f3552ed250a179.json"}}, {"family": "Huber", "given": "Wolfgang", "initials": "W"}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Colomer", "given": "Dolors", "initials": "D", "orcid": "0000-0001-7486-8484", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e7b74af349aa4e269efeaa45181afeb6.json"}}, {"family": "Mart\u00edn-Subero", "given": "Jos\u00e9 I", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}, {"family": "Delgado", "given": "Julio", "initials": "J", "orcid": "0000-0002-5157-4376", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c8bb41dc1fdf4709b6c193df84127af8.json"}}, {"family": "Morin", "given": "Ryan D", "initials": "RD", "orcid": "0000-0003-2932-7800", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f6f69a934a0a40faa7939021e304276d.json"}}, {"family": "Stein", "given": "Lincoln D", "initials": "LD"}, {"family": "Puente", "given": "Xose S", "initials": "XS", "orcid": "0000-0001-9525-1483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0.json"}}, {"family": "Campo", "given": "El\u00edas", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}], "type": "journal article", "published": "2025-09-00", "journal": {"title": "Leukemia", "issn": "1476-5551", "volume": "39", "issue": "9", "pages": "2076-2086", "issn-l": "0887-6924"}, "abstract": "Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas. We confirmed that the g.3A>C U1 mutation is found in 3.5% of CLL, which conferred rapid disease progression independently of the main biological and clinical prognostic markers of the disease. Additionally, a recurrent g.9C>T mutation was found in 1.5% of CLL causing downstream splicing alterations and associated with adverse prognosis. We also identified a g.4C>T mutation in 10% of diffuse large B-cell lymphomas of the germinal center subtype and a g.7A>G mutation in 30% of EBV-negative Burkitt lymphomas, both of which altered the splicing pattern of multiple genes. This study reveals novel, recurrent, and tumor-specific U1 mutations in mature B-cell neoplasms with biological and prognostic implications, thus establishing U1 as a novel pan-B-cell malignancy driver gene.", "doi": "10.1038/s41375-025-02667-7", "pmid": "40588565", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12380619"}, {"db": "pii", "key": "10.1038/s41375-025-02667-7"}], "notes": [], "created": "2026-09-23T13:18:58.441Z", "modified": "2026-09-23T13:18:59.106Z"}, {"entity": "publication", "iuid": "1111a4bf4db94540a40538bad3642238", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1111a4bf4db94540a40538bad3642238.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1111a4bf4db94540a40538bad3642238"}}, "title": "BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib.", "authors": [{"family": "Bonfiglio", "given": "Silvia", "initials": "S", "orcid": "0000-0002-4422-1580", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/162be08efd064fddb70eeda159cf7ddd.json"}}, {"family": "Sutton", "given": "Lesley-Ann", "initials": "LA"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Capasso", "given": "Antonella", "initials": "A"}, {"family": "Pandzic", "given": "Tatjana", "initials": "T"}, {"family": "Westr\u00f6m", "given": "Simone", "initials": "S"}, {"family": "Foroughi-Asl", "given": "Hassan", "initials": "H"}, {"family": "Skaftason", "given": "Aron", "initials": "A"}, {"family": "Gellerbring", "given": "Anna", "initials": "A"}, {"family": "Lyander", "given": "Anna", "initials": "A"}, {"family": "Gandini", "given": "Francesca", "initials": "F", "orcid": "0000-0001-8930-8295", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/849fd1abee01405090fd7f5deac39523.json"}}, {"family": "Gaidano", "given": "Gianluca", "initials": "G", "orcid": "0000-0002-4681-0151", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8c61a087170e49ae9f062617c751153e.json"}}, {"family": "Trentin", "given": "Livio", "initials": "L", "orcid": "0000-0003-1222-6149", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/820ab4c1a5534ada88d9c318fa8aa2e1.json"}}, {"family": "Bonello", "given": "Lisa", "initials": "L"}, {"family": "Reda", "given": "Gianluigi", "initials": "G"}, {"family": "B\u00f6d\u00f6r", "given": "Csaba", "initials": "C"}, {"family": "Stavroyianni", "given": "Niki", "initials": "N"}, {"family": "Tam", "given": "Constantine S", "initials": "CS", "orcid": "0000-0002-9759-5017", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5754a0b1fb864629b48bdd59c515dffc.json"}}, {"family": "Marasca", "given": "Roberto", "initials": "R", "orcid": "0000-0002-6431-6878", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5424e54c248d47d08e88f019dc560f9b.json"}}, {"family": "Forconi", "given": "Francesco", "initials": "F", "orcid": "0000-0002-2211-1831", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e20e20e4662a45559771aa3fabb8108d.json"}}, {"family": "Panayiotidis", "given": "Panayiotis", "initials": "P", "orcid": "0000-0003-0387-3993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f7085c2ef7744b480e7c936160d1680.json"}}, {"family": "Ringshausen", "given": "Ingo", "initials": "I", "orcid": "0000-0002-7247-311X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1f0a81b9b0334999b6c4a2f263c719f4.json"}}, {"family": "Jaksic", "given": "Ozren", "initials": "O"}, {"family": "Frustaci", "given": "Anna Maria", "initials": "AM", "orcid": "0000-0003-2587-7901", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d22c0b39c6f54eb88fd67cfe64c377d0.json"}}, {"family": "Iyengar", "given": "Sunil", "initials": "S", "orcid": "0000-0003-4863-4160", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2cabdec0706e4120ad2ffb952270318d.json"}}, {"family": "Coscia", "given": "Marta", "initials": "M", "orcid": "0000-0003-2123-7675", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6bbe65e7e5cf4d0eaebff1209a434c15.json"}}, {"family": "Mulligan", "given": "Stephen P", "initials": "SP"}, {"family": "Ysebaert", "given": "Lo\u00efc", "initials": "L"}, {"family": "Strugov", "given": "Vladimir", "initials": "V"}, {"family": "Pavlovsky", "given": "Carolina", "initials": "C"}, {"family": "Walewska", "given": "Renata", "initials": "R"}, {"family": "\u00d6sterborg", "given": "Anders", "initials": "A"}, {"family": "Cortese", "given": "Diego", "initials": "D"}, {"family": "Ranghetti", "given": "Pamela", "initials": "P"}, {"family": "Baliakas", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-5634-7156", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2a31997db1ee4ef1aaff75e423b8ccfb.json"}}, {"family": "Stamatopoulos", "given": "Kostas", "initials": "K", "orcid": "0000-0001-8529-640X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06f6107d6f774ee6acb2c66ecfcb90cc.json"}}, {"family": "Scarf\u00f2", "given": "Lydia", "initials": "L", "orcid": "0000-0002-0844-0989", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/7697d7b279ae48a387843c617f30fa3c.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-9067-9058", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5de185945f944434aa914fa39cfdb97f.json"}}, {"family": "Ghia", "given": "Paolo", "initials": "P", "orcid": "0000-0003-3750-7342", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/475d35f1a3c446819b2f24be819c2dee.json"}}], "type": "observational study", "published": "2023-06-27", "journal": {"title": "Blood Adv", "issn": "2473-9529", "volume": "7", "issue": "12", "pages": "2794-2806", "issn-l": null}, "abstract": "Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after \u22651 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital polymerase chain reaction (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32 of 49 relapsing cases (65%) carried at least 1 hotspot BTK and/or PLCG2 mutation(s); in 6 of 32, BTK mutations were only detected by ddPCR (variant allele frequency [VAF] 0.1% to 1.2%). BTK/PLCG2 mutations were also identified in 6 of 49 responding patients (12%; 5/6 VAF <10%), of whom 2 progressed later. Among the relapsing patients, the BTK-mutated (BTKmut) group was enriched for EGR2 mutations, whereas BTK-wildtype (BTKwt) cases more frequently displayed BIRC3 and NFKBIE mutations. Using an extended capture-based panel, only BRAF and IKZF3 mutations showed a predominance in relapsing cases, who were enriched for del(8p) (n = 11; 3 BTKwt). Finally, no difference in TP53 mutation burden was observed between BTKmut and BTKwt relapsing cases, and ibrutinib treatment did not favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance.", "doi": "10.1182/bloodadvances.2022008821", "pmid": "36696464", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10279547"}, {"db": "pii", "key": "494230"}], "notes": [], "created": "2026-09-23T08:36:47.686Z", "modified": "2026-09-23T08:36:48.424Z"}]}