title: Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia.
abstract: Here we perform whole-exome sequencing of samples from 105 individuals with chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries. We found 1,246 somatic mutations potentially affecting gene function and identified 78 genes with predicted functional alterations in more than one tumor sample. Among these genes, SF3B1, encoding a subunit of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), is somatically mutated in 9.7% of affected individuals. Further analysis in 279 individuals with CLL showed that SF3B1 mutations were associated with faster disease progression and poor overall survival. This work provides the first comprehensive catalog of somatic mutations in CLL with relevant clinical correlates and defines a large set of new genes that may drive the development of this common form of leukemia. The results reinforce the idea that targeting several well-known genetic pathways, including mRNA splicing, could be useful in the treatment of CLL and other malignancies.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Quesada
authors.forename: Laura
authors.initials: L
authors.lastname: Conde
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Gonzalo R
authors.initials: GR
authors.lastname: Ordóñez
authors.forename: Pedro
authors.initials: P
authors.lastname: Jares
authors.forename: Laia
authors.initials: L
authors.lastname: Bassaganyas
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ramsay
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
authors.forename: Magda
authors.initials: M
authors.lastname: Pinyol
authors.forename: Alejandra
authors.initials: A
authors.lastname: Martínez-Trillos
authors.forename: Mónica
authors.initials: M
authors.lastname: López-Guerra
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.forename: Tycho
authors.initials: T
authors.lastname: Baumann
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: María
authors.initials: M
authors.lastname: Rozman
authors.forename: Julio
authors.initials: J
authors.lastname: Delgado
authors.forename: Eva
authors.initials: E
authors.lastname: Giné
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández
authors.forename: Marcos
authors.initials: M
authors.lastname: González-Díaz
authors.forename: Diana A
authors.initials: DA
authors.lastname: Puente
authors.forename: Gloria
authors.initials: G
authors.lastname: Velasco
authors.forename: José M P
authors.initials: JM
authors.lastname: Freije
authors.forename: José M C
authors.initials: JM
authors.lastname: Tubío
authors.forename: Romina
authors.initials: R
authors.lastname: Royo
authors.forename: Josep L
authors.initials: JL
authors.lastname: Gelpí
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Jorge
authors.initials: J
authors.lastname: Zamora
authors.forename: Miguel
authors.initials: M
authors.lastname: Vázquez
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.forename: Heinz
authors.initials: H
authors.lastname: Himmelbauer
authors.forename: Mónica
authors.initials: M
authors.lastname: Bayés
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Xose S
authors.initials: XS
authors.lastname: Puente
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D000595:Amino Acid Sequence; D018450:Disease Progression; D059472:Exome; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000401:mortality; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human