EGAGenomicsN/Ahttps://ega-archive.org/datasets/EGAD000100008750EGA dataset EGAD00010000875EGAChronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases and 54 patients with monoclonal B-lymphocytosis, a precursor disorder. We extend the number of CLL driver alterations, including changes in ZNF292, ZMYM3, ARID1A and PTPN11. We also identify novel recurrent mutations in non-coding regions, including the 3' region of NOTCH1, which cause aberrant splicing events, increase NOTCH1 activity and result in a more aggressive disease. In addition, mutations in an enhancer located on chromosome 9p13 result in reduced expression of the B-cell-specific transcription factor PAX5. The accumulative number of driver alterations (0 to ≥4) discriminated between patients with differences in clinical behaviour. This study provides an integrated portrait of the CLL genomic landscape, identifies new recurrent driver mutations of the disease, and suggests clinical interventions that may improve the management of this neoplasia.Non-coding recurrent mutations in chronic lymphocytic leukaemia.Puente Xose S XS, Beà Silvia S, Valdés-Mas Rafael R, Villamor Neus N, Gutiérrez-Abril Jesús J, Martín-Subero José I JI, Munar Marta M, Rubio-Pérez Carlota C, Jares Pedro P, Aymerich Marta M, Baumann Tycho T, Beekman Renée R, Belver Laura L, Carrio Anna A, Castellano Giancarlo G, Clot Guillem G, Colado Enrique E, Colomer Dolors D, Costa Dolors D, Delgado Julio J, Enjuanes Anna A, Estivill Xavier X, Ferrando Adolfo A AA, Gelpí Josep L JL, González Blanca B, González Santiago S, González Marcos M, Gut Marta M, Hernández-Rivas Jesús M JM, López-Guerra Mónica M, Martín-García David D, Navarro Alba A, Nicolás Pilar P, Orozco Modesto M, Payer Ángel R ÁR, Pinyol Magda M, Pisano David G DG, Puente Diana A DA, Queirós Ana C AC, Quesada Víctor V, Romeo-Casabona Carlos M CM, Royo Cristina C, Royo Romina R, Rozman María M, Russiñol Nuria N, Salaverría Itziar I, Stamatopoulos Kostas K, Stunnenberg Hendrik G HG, Tamborero David D, Terol María J MJ, Valencia Alfonso A, López-Bigas Nuria N, Torrents David D, Gut Ivo I, López-Guillermo Armando A, López-Otín Carlos C, Campo Elías Eleukemia, CLL, Cll, small lymphocytic lymphoma, c15, B-cell chronic lymphocytic leukemia, DmelCG7937, CG7937., Chronic Lymphocytic Leukemia, chronic LYMPHOCYTIC, lymphoplasmacytic leukaemia, 311, lymphoplasmacytic leukemia, adult chronic leukaemia, chronic, B-cell chronic lymphocytic leukaemia, Ect5, cll, CML, Hox11-311, 93Bal, B-cell chronic lymphoid leukemia, adult chronic leukemia, microarray, chronic lymphocytic leukaemia, chronic lymphatic leukemia, lymphocytic, chronic lymphatic leukaemia, chronic lymphaticleukemia, CLL, Cll, small lymphocytic lymphoma, c15, B-cell chronic lymphocytic leukemia, DmelCG7937, Chronic Lymphocytic Leukemia, chronic LYMPHOCYTIC, lymphoplasmacytic leukaemia, 311, lymphoplasmacytic leukemia, adult chronic leukaemia, chronic, B-cell chronic lymphocytic leukaemia, Ect5, cll, CML, Hox11-311, 93Bal, microarray., B-cell chronic lymphoid leukemia, adult chronic leukemia, chronic lymphocytic leukaemia, chronic lymphatic leukemia, lymphocytic, chronic lymphatic leukaemia, chronic lymphatic, CG7937Mutations, Chronic.CLL, Cll, other disease, atypia, SHPTP2, xnotch, nuclear mRNA cis splicing, Activity, hN1, region or site annotation, NS1, KLP, Neoplasms, number, Benign Neoplasm, chronic LYMPHOCYTIC, Smarcf1, precursor, Tumor, Zn-15, Malignant, B-cell chronic lymphocytic leukaemia, P270, MYM, Mutations, cll, CML, BAF250a, hELD, Znf292, NOTCH, diseases, reduced, B-cell chronic lymphoid leukemia, disease or disorder, diseases and disorders, SHP-2, ZFP292, atypical, tiny, notch, chronic lymphatic, CFC, EBB-1, study, positional, human disease, ZN-16, B-cell-specific transcription factor, B-cell chronic lymphocytic leukemia, Malignancy, BAF250, hypoplasia, chromatid, SAP-2, adult chronic leukaemia, Ect5, BSAP, non-neoplastic, genetic, Neoplasias, ZNF261, geographical area, via U2-type spliceosome, high frequency, notch1-a, Clients, Xotch, adult chronic leukemia, PTP1D, Chronic, disorder, Homo sapiens disease, Malignancies, T14, chronic lymphatic leukaemia, constitutitional genetic, ELD, CG7937, SH-PTP3, single-organism behavior, SH-PTP2, Cancer, Tumors, small, leukemia, hOSA1, SMARCF1, AW536184, Malignant Neoplasm, BM029, aberrant, Chronic Lymphocytic Leukemia, disorders, familial, lymphoplasmacytic leukaemia, 311, PTP2C, 9930111A19Rik, medical condition, defective, lin-12, lymphoplasmacytic leukemia, Client, PTP-1D, chronic, N1, prophase chromosome, Motch, Benign, 93Bal, Syp, PAX5, 1110030E03Rik, Diseases, Neoplasm, Lymphocytoses, sequence, condition, B120, chronic lymphatic leukemia, ZNF198L2, lymphocytic, XFIM, INSDC_feature:regulatory, parent ion, MRD14, xnotch1, small lymphocytic lymphoma, C1orf4, c15, frequent, positional polypeptide feature, underdeveloped, ALL3, interphase chromosome, DmelCG7937, 2700084A17Rik, Shp2, Osa1, OSA1, SHP2, Benign Neoplasms, Cancers, primary structure of sequence macromolecule, DXS6673E, disease, Hox11-311, Nbla00365, precursor ion, Patient, Chromosome, Portraits, AOVD1, bA393I2.3, cardinality, BPTP3, AOS5, ptp-2, chronic lymphocytic leukaemia, inherited genetic, notch-1, TAN1, Tan1, other neoplasm, hereditary, Pax-5, Mis6, General activity, Neoplasia, Malignant Neoplasms.falseU219-array-CLL-EGAS00001001306CLL Expression Array2022-08-19 13:29:49EGAD00010000875960626200345EGAC00001000010EGAS00001001306