Genetics of follicular lymphoma transformation.

TitleGenetics of follicular lymphoma transformation.
Publication TypeJournal Article
Year of Publication2014
AuthorsPasqualucci L, Khiabanian H, Fangazio M, Vasishtha M, Messina M, Holmes AB, Ouillette P, Trifonov V, Rossi D, Tabbo F, Ponzoni M, Chadburn A, Murty VV, Bhagat G, Gaidano G, Inghirami G, Malek SN, Rabadan R, Dalla-Favera R
JournalCell Rep
Volume6
Issue1
Pagination130-40
Date Published2014 Jan 16
ISSN2211-1247
KeywordsApoptosis, Carcinogenesis, Epigenesis, Genetic, Evolution, Molecular, Genes, myc, Genes, p16, Genes, p53, Humans, Lymphoma, Follicular, Mutation
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) 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.

DOI10.1016/j.celrep.2013.12.027
Alternate JournalCell Rep
PubMed ID24388756
PubMed Central IDPMC4100800
Grant ListU54-AI057158 / AI / NIAID NIH HHS / United States
R01-CA136537 / CA / NCI NIH HHS / United States
1R01LM010140-01 / LM / NLM NIH HHS / United States
R01-CA172492-01 / CA / NCI NIH HHS / United States
R01-CA37295 / CA / NCI NIH HHS / United States
Related Faculty: 
Giorgio Inghirami, M.D.

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