{"entity": "researcher", "timestamp": "2026-09-26T00:43:34.906Z", "family": "Puente", "given": "Xos\u00e9 S", "initials": "XS", "orcid": "0000-0001-9525-1483", "affiliations": ["Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer, CIBERONC, Madrid, Spain.", "Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Instituto Universitario de Oncolog\u00eda (IUOPA), Universidad de Oviedo, Oviedo, Spain."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0"}}, "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": "b1f32b202ed34b26b5360370a45c1125", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b1f32b202ed34b26b5360370a45c1125.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b1f32b202ed34b26b5360370a45c1125"}}, "title": "The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome.", "authors": [{"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf156c05415b4ca68ef16154910405e8.json"}}, {"family": "Clot", "given": "Guillem", "initials": "G"}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50c437deb106439282f36834216b320a.json"}}, {"family": "Beekman", "given": "Ren\u00e9e", "initials": "R"}, {"family": "Baumann", "given": "Tycho", "initials": "T"}, {"family": "Nordlund", "given": "Jessica", "initials": "J"}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Rivas-Delgado", "given": "Alfredo", "initials": "A", "orcid": "0000-0003-0385-3415", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6806e38bd303403ea24422bfcb5da908.json"}}, {"family": "Mart\u00edn", "given": "Silvia", "initials": "S"}, {"family": "Ordo\u00f1ez", "given": "Raquel", "initials": "R"}, {"family": "Castellano", "given": "Giancarlo", "initials": "G"}, {"family": "Kulis", "given": "Marta", "initials": "M"}, {"family": "Queir\u00f3s", "given": "Ana C", "initials": "AC"}, {"family": "Lee", "given": "Seung-Tae", "initials": "ST"}, {"family": "Wiemels", "given": "Joseph", "initials": "J"}, {"family": "Royo", "given": "Romina", "initials": "R"}, {"family": "Puiggr\u00f3s", "given": "Montserrat", "initials": "M", "orcid": "0000-0001-5034-7924", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed1bc769f28948d392125868cde7f2ab.json"}}, {"family": "Lu", "given": "Junyan", "initials": "J"}, {"family": "Gin\u00e9", "given": "Eva", "initials": "E"}, {"family": "Be\u00e0", "given": "S\u00edlvia", "initials": "S"}, {"family": "Jares", "given": "Pedro", "initials": "P", "orcid": "0000-0002-8401-579X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/30b5499dd6294010ad4db36440df44d1.json"}}, {"family": "Agirre", "given": "Xabier", "initials": "X", "orcid": "0000-0002-6558-9560", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e414cbce67124d808e0067db341966ce.json"}}, {"family": "Prosper", "given": "Felipe", "initials": "F"}, {"family": "L\u00f3pez-Ot\u00edn", "given": "Carlos", "initials": "C", "orcid": "0000-0001-6964-1904", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/28e557a76f8b43b29f6d649823f40e5a.json"}}, {"family": "Puente", "given": "Xos\u00e9 S", "initials": "XS", "orcid": "0000-0001-9525-1483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0.json"}}, {"family": "Oakes", "given": "Christopher C", "initials": "CC"}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/13160825496147c897b8d57be3a61caa.json"}}, {"family": "Delgado", "given": "Julio", "initials": "J"}, {"family": "L\u00f3pez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Campo", "given": "El\u00edas", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/027ab2ad72e7442da10e441a24100503.json"}}, {"family": "Mart\u00edn-Subero", "given": "Jos\u00e9 Ignacio", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d6b1944a98214848b864342473012567.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "volume": "1", "issue": "11", "pages": "1066-1081", "issn-l": null}, "abstract": "We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.", "doi": "10.1038/s43018-020-00131-2", "pmid": "34079956", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1700108"}, {"db": "pmc", "key": "PMC8168619"}, {"db": "pii", "key": "10.1038/s43018-020-00131-2"}], "notes": [], "created": "2026-09-23T07:40:12.554Z", "modified": "2026-09-23T07:40:12.956Z"}, {"entity": "publication", "iuid": "05d98747307c46afa804634a4a558d67", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/05d98747307c46afa804634a4a558d67.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/05d98747307c46afa804634a4a558d67"}}, "title": "Germline variation in the oxidative DNA repair genes NUDT1 and OGG1 is not associated with hereditary colorectal cancer or polyposis.", "authors": [{"family": "Mur", "given": "Pilar", "initials": "P", "orcid": "0000-0003-0780-926X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f067ce8023a74844bf8112ef3c89df1e.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/51f26d370fb74994b8e2b4fa1c9c2f7a.json"}}, {"family": "Bevc", "given": "Luka", "initials": "L"}, {"family": "Amaral", "given": "Nuno", "initials": "N"}, {"family": "Navarro", "given": "Matilde", "initials": "M"}, {"family": "Vald\u00e9s-Mas", "given": "Rafael", "initials": "R"}, {"family": "Pons", "given": "Tirso", "initials": "T", "orcid": "0000-0002-7616-7750", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b71a71d52a424f7a990ae60b3db86fa1.json"}}, {"family": "Aiza", "given": "Gemma", "initials": "G"}, {"family": "Urioste", "given": "Miguel", "initials": "M"}, {"family": "Valencia", "given": "Alfonso", "initials": "A", "orcid": "0000-0002-8937-6789", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/80973e7b48094490adf93726d44c49b1.json"}}, {"family": "L\u00e1zaro", "given": "Conxi", "initials": "C", "orcid": "0000-0002-7198-5906", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d0baaa341dde4402a5f4ac91886e5d14.json"}}, {"family": "Moreno", "given": "Victor", "initials": "V", "orcid": "0000-0002-2818-5487", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/32aed9ffc52445f88e623083bf2f5906.json"}}, {"family": "Puente", "given": "Xose S", "initials": "XS", "orcid": "0000-0001-9525-1483", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/682af7b4d9624247b095cb285b54a4c0.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9791bc0d7463417899d6953b5ca1bac3.json"}}, {"family": "Warpman-Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Capell\u00e1", "given": "Gabriel", "initials": "G", "orcid": "0000-0002-4669-7320", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eb3628d2354f4c3cbef1b7cf82305cff.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/385586c159494955a9a72c3381e3ad47.json"}}, {"family": "Valle", "given": "Laura", "initials": "L", "orcid": "0000-0003-0371-0844", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/977e9239650f4b05be734dc6a9c1c899.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "39", "issue": "9", "pages": "1214-1225", "issn-l": "1059-7794"}, "abstract": "The causal association of NUDT1 (=MTH1) and OGG1 with hereditary colorectal cancer (CRC) remains unclear. Here, we sought to provide additional evidence for or against the causal contribution of NUDT1 and OGG1 mutations to hereditary CRC and/or polyposis. Mutational screening was performed using pooled DNA amplification and targeted next-generation sequencing in 529 families (441 uncharacterized MMR-proficient familial nonpolyposis CRC and 88 polyposis cases). Cosegregation, in silico analyses, in vitro functional assays, and case-control associations were carried out to characterize the identified variants. Five heterozygous carriers of novel (n = 1) or rare (n = 4) NUDT1 variants were identified. In vitro deleterious effects were demonstrated for c.143G>A p.G48E (catalytic activity and protein stability) and c.403G>T p.G135W (protein stability), although cosegregation data in the carrier families were inconclusive or nonsupportive. The frequency of missense, loss-of-function, and splice-site NUDT1 variants in our familial CRC cohort was similar to the one observed in cancer-free individuals, suggesting lack of association with CRC predisposition. No OGG1 pathogenic mutations were identified. Our results suggest that the contribution of NUDT1 and OGG1 germline mutations to hereditary CRC and to polyposis is inexistent or, at most, negligible. The inclusion of these genes in routine genetic testing is not recommended.", "doi": "10.1002/humu.23564", "pmid": "29900613", "labels": [], "xrefs": [], "notes": [], "created": "2019-01-17T14:01:11.985Z", "modified": "2026-09-23T12:47:47.665Z"}]}