Recurrent Gene Mutations in CLL

  • Alejandra Martínez-Trillos
  • Víctor Quesada
  • Neus Villamor
  • Xose S. Puente
  • Carlos López-Otín
  • Elías CampoEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 792)


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.


Chronic lymphocytic leukemia Next-generation sequencing Somatic mutations NOTCH1 SF3B1 MYD88 



The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTICC) del ISCIII. We are grateful to the members of our groups for their contribution to the studies of the consortium and N. Villahoz and M.C. Muro for their excellent work in the coordination of the CLL Spanish Consortium.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Alejandra Martínez-Trillos
    • 1
  • Víctor Quesada
    • 2
  • Neus Villamor
    • 1
  • Xose S. Puente
    • 2
  • Carlos López-Otín
    • 2
  • Elías Campo
    • 3
    Email author
  1. 1.Unidad de Hematopatologia, Departamento de Anatomía Patológica, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS)Universitat de BarcelonaBarcelonaSpain
  2. 2.Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología-IUOPAUniversidad de OviedoOviedoSpain
  3. 3.Hematopathology Unit, Hospital ClinicUniversity of BarcelonaBarcelonaSpain

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