title: Recurrent gene mutations in CLL.
abstract: Next-generation sequencing of whole genomes and exomes in chronic lymphocytic leukemia (CLL) has provided the first comprehensive view of somatic mutations in this disease. Subsequent studies have characterized the oncogenic pathways and clinical implications of a number of these mutations. The global number of somatic mutations per case is lower than those described in solid tumors but is in agreement with previous estimates of less than one mutation per megabase in hematological neoplasms. The number and pattern of somatic mutations differ in tumors with unmutated and mutated IGHV, extending at the genomic level the clinical differences observed in these two CLL subtypes. One of the striking conclusions of these studies has been the marked genetic heterogeneity of the disease, with a relatively large number of genes recurrently mutated at low frequency and only a few genes mutated in up to 10-15 % of the patients. The mutated genes tend to cluster in different pathways that include NOTCH1 signaling, RNA splicing and processing machinery, innate inflammatory response, Wnt signaling, and DNA damage and cell cycle control, among others. These results highlight the molecular heterogeneity of CLL and may provide new biomarkers and potential therapeutic targets for the diagnosis and management of the disease.
authors.affiliation: Unidad de Hematopatologia, Departamento de Anatomía Patológica, Hospital Clinic, Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez-Trillos
authors.forename: Víctor
authors.initials: V
authors.lastname: Quesada
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Xose S
authors.initials: XS
authors.lastname: Puente
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
mesh_terms: D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics
chemical_list: D053594:Myeloid Differentiation Factor 88; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human