Exome Sequencing Identifies Recurrent Mutations of the Splicing Factor SF3B1 Gene in Chronic Lymphocytic Leukemia

Overview

Journal Nat Genet

Specialty Genetics

Date 2011 Dec 14

PMID 22158541

Citations 512

Authors

Victor Quesada

Laura Conde

Neus Villamor

Gonzalo R Ordonez

Pedro Jares

Laia Bassaganyas

Andrew J Ramsay

Silvia Bea

Magda Pinyol

Alejandra Martinez-Trillos

Monica Lopez-Guerra

Dolors Colomer

Alba Navarro

Tycho Baumann

Marta Aymerich

Maria Rozman

Julio Delgado

Eva Gine

Jesus M Hernandez

Marcos Gonzalez-Diaz

Diana A Puente

Gloria Velasco

Jose M P Freije

Jose M C Tubio

Romina Royo

Josep L Gelpi

Modesto Orozco

David G Pisano

Jorge Zamora

Miguel Vazquez

Alfonso Valencia

Heinz Himmelbauer

Monica Bayes

Simon Heath

Marta Gut

Ivo Gut

Xavier Estivill

Armando Lopez-Guillermo

Xose S Puente

Elias Campo

Carlos Lopez-Otin

Affiliations

Soon will be listed here.

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.

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