Genetics of Follicular Lymphoma Transformation

Laura Pasqualucci; Hossein Khiabanian; Marco Fangazio; Mansi Vasishtha; Monica Messina; Antony B. Holmes; Peter Ouillette; Vladimir Trifonov; Davide Rossi; Fabrizio Tabbò; Maurilio Ponzoni; Amy Chadburn; Vundavalli V. Murty; Govind Bhagat; Gianluca Gaidano; Giorgio Inghirami; Sami N. Malek; Raul Rabadan; Riccardo Dalla-Favera

doi:10.1016/j.celrep.2013.12.027

Cell Reports (Jan 2014)

Genetics of Follicular Lymphoma Transformation

Laura Pasqualucci,
Hossein Khiabanian,
Marco Fangazio,
Mansi Vasishtha,
Monica Messina,
Antony B. Holmes,
Peter Ouillette,
Vladimir Trifonov,
Davide Rossi,
Fabrizio Tabbò,
Maurilio Ponzoni,
Amy Chadburn,
Vundavalli V. Murty,
Govind Bhagat,
Gianluca Gaidano,
Giorgio Inghirami,
Sami N. Malek,
Raul Rabadan,
Riccardo Dalla-Favera

Affiliations

Laura Pasqualucci: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Hossein Khiabanian: Department of Biomedical Informatics and Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA
Marco Fangazio: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Mansi Vasishtha: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Monica Messina: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Antony B. Holmes: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Peter Ouillette: Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA
Vladimir Trifonov: Department of Biomedical Informatics and Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA
Davide Rossi: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara 28100, Italy
Fabrizio Tabbò: Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino 10126, Italy
Maurilio Ponzoni: Pathology and Lymphoid Malignancies Units, San Raffaele Scientific Institute, Milan 20132, Italy
Amy Chadburn: Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Vundavalli V. Murty: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA
Govind Bhagat: Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
Gianluca Gaidano: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara 28100, Italy
Giorgio Inghirami: Department of Molecular Biotechnology and Health Science, Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino 10126, Italy
Sami N. Malek: Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA
Raul Rabadan: Department of Biomedical Informatics and Center for Computational Biology and Bioinformatics, Columbia University, New York, NY 10032, USA
Riccardo Dalla-Favera: Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA

DOI: https://doi.org/10.1016/j.celrep.2013.12.027
Journal volume & issue: Vol. 6, no. 1
pp. 130 – 140

Abstract

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Follicular lymphoma (FL) is an indolent disease, but 30%–40% of cases undergo histologic transformation to an aggressive malignancy, typically represented by diffuse large B cell lymphoma (DLBCL). The pathogenesis of this process remains largely unknown. Using whole-exome sequencing and copy-number analysis, we show here that the dominant clone of FL and transformed FL (tFL) arise by divergent evolution from a common mutated precursor through the acquisition of distinct genetic events. Mutations in epigenetic modifiers and antiapoptotic genes are introduced early in the common precursor, whereas tFL is specifically associated with alterations deregulating cell-cycle progression and DNA damage responses (CDKN2A/B, MYC, and TP53) as well as aberrant somatic hypermutation. The genomic profile of tFL shares similarities with that of germinal center B cell-type de novo DLBCL but also displays unique combinations of altered genes with diagnostic and therapeutic implications.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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