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Genetic and epigenetic determinants of B-cell lymphoma evolution

Izzo, Franco; Landau, Dan A.

Current Opinion in Hematology: July 2016 - Volume 23 - Issue 4 - p 392–401
doi: 10.1097/MOH.0000000000000258

Purpose of review The success of targeted therapies fostered the development of increasingly specific and effective therapeutics for B-cell malignancies. However, cancer plasticity facilitates disease relapse, whereby intratumoral heterogeneity fuels tumor evolution into a more aggressive and resistant form. Understanding cancer heterogeneity and the evolutionary processes underlying disease relapse is key for overcoming this limitation of current treatment strategies. In the present review, we delineate the current understanding of cancer evolution and the advances in both genetic and epigenetic fields, with a focus on non-Hodgkin B-cell lymphomas.

Recent findings The use of massively parallel sequencing has provided insights into tumor heterogeneity, allowing determination of intratumoral genetic and epigenetic variability and identification of cancer driver mutations and (epi-)mutations. Increased heterogeneity prior to treatment results in faster disease relapse, and in many cases studying pretreatment clonal admixtures predicts the future evolutionary trajectory of relapsed disease.

Summary Understanding the mechanisms underlying tumor heterogeneity and evolution provides valuable tools for the design of therapy within an evolutionary framework. This framework will ultimately aid in accurately predicting the evolutionary paths of B-cell malignancies, thereby guiding therapeutic strategies geared at directly anticipating and addressing cancer evolution.

aMeyer Cancer Center, Weill Cornell Medicine

bNew York Genome Center, New York, New York, USA

cInstituto de Biología y Medicina Experimental (IBYME), CONICET, Buenos Aires, Argentina

Correspondence to Dan A. Landau, MD, PhD, New York Genome Center, 101 Avenue of the Americas, Room 621, New York, NY 10013, USA. E-mail:

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