@article{eec40d5028bf4353943dc846f238e0ee,
title = "Genetics of Follicular Lymphoma Transformation",
abstract = "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) aswell 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.",
author = "Laura Pasqualucci and Hossein Khiabanian and Marco Fangazio and Mansi Vasishtha and Monica Messina and Holmes, \{Antony B.\} and Peter Ouillette and Vladimir Trifonov and Davide Rossi and Fabrizio Tabb{\`o} and Maurilio Ponzoni and Amy Chadburn and Murty, \{Vundavalli V.\} and Govind Bhagat and Gianluca Gaidano and Giorgio Inghirami and Malek, \{Sami N.\} and Raul Rabadan and Riccardo Dalla-Favera",
note = "Funding Information: We thank G. Fabbri for discussions, V. Miljkovic for help with the SNP array hybridization, and the Molecular Pathology Shared Resource and the Molecular Cytogenetics and Epigenetics Shared Resource of the Herbert Irving Comprehensive Cancer Center at Columbia University for histology service and cytogenetics service, respectively. We also thank R. Feldman and R. Mei for expert assistance with the whole-exome capture and sequencing, which were completed at Centrillion Biosciences. Automated DNA sequencing was performed at GENEWIZ. This work was supported by the NIH (RO1-CA37295 to R.D.-F., RO1-CA172492-01 to L.P., and RO1-CA136537 to S.N.M.), a Specialized Center of Research grant from the Leukemia \& Lymphoma Society (to R.D.-F.), the Northeast Biodefense Center (U54-AI057158), and the National Library of Medicine (1R01LM010140-01 to R.R.), the AIRC Special Program Molecular Clinical Oncology – 5 per mille (contract 10007 to G.G. and G.I.), and the Cariplo Foundation (to G.G.). L.P. is on leave from the Institute of Hematology, University of Perugia Medical School. M.F. was enrolled in the PhD program in Clinical and Experimental Medicine at Amedeo Avogadro University of Eastern Piedmont and was supported in part by the Novara AIL. ",
year = "2014",
doi = "10.1016/j.celrep.2013.12.027",
language = "English",
volume = "6",
pages = "130--140",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}