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Recurrent Gene Mutations in CLL

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Book cover Advances in Chronic Lymphocytic Leukemia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 792))

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.

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Acknowledgements

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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Authors and Affiliations

  1. Unidad de Hematopatologia, Departamento de Anatomía Patológica, Hospital Clinic, Institut d’Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain

    Alejandra Martínez-Trillos & Neus Villamor

  2. Departamento de Bioquímica y Biología Molecular, Instituto Universitario de Oncología-IUOPA, Universidad de Oviedo, Oviedo, Spain

    Víctor Quesada, Xose S. Puente & Carlos López-Otín

  3. Hematopathology Unit, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, 08015, Spain

    Elías Campo

Authors
  1. Alejandra Martínez-Trillos
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  2. Víctor Quesada
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  3. Neus Villamor
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  4. Xose S. Puente
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  5. Carlos López-Otín
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  6. Elías Campo
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Correspondence to Elías Campo .

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Editors and Affiliations

  1. Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Sami Malek

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Martínez-Trillos, A., Quesada, V., Villamor, N., Puente, X.S., López-Otín, C., Campo, E. (2013). Recurrent Gene Mutations in CLL. In: Malek, S. (eds) Advances in Chronic Lymphocytic Leukemia. Advances in Experimental Medicine and Biology, vol 792. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8051-8_4

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