Genetics of Follicular Lymphoma Transformation

Laura Pasqualucci, Hossein Khiabanian, Marco Fangazio, Mansi Vasishtha, Monica Messina, AntonyB Holmes, Peter Ouillette, Vladimir Trifonov, Davide Rossi, Fabrizio Tabbò, Maurilio Ponzoni, Amy Chadburn, VundavalliV Murty, Govind Bhagat, Gianluca Gaidano, Giorgio Inghirami, SamiN Malek, Raul Rabadan, Riccardo Dalla-Favera

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)130-140
Number of pages11
JournalCell Reports
Volume6
Issue number1
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pasqualucci, L., Khiabanian, H., Fangazio, M., Vasishtha, M., Messina, M., Holmes, A., Ouillette, P., Trifonov, V., Rossi, D., Tabbò, F., Ponzoni, M., Chadburn, A., Murty, V., Bhagat, G., Gaidano, G., Inghirami, G., Malek, S., Rabadan, R., & Dalla-Favera, R. (2014). Genetics of Follicular Lymphoma Transformation. Cell Reports, 6(1), 130-140. https://doi.org/10.1016/j.celrep.2013.12.027