Title | Genetics of follicular lymphoma transformation. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Pasqualucci 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 |
Journal | Cell Rep |
Volume | 6 |
Issue | 1 |
Pagination | 130-40 |
Date Published | 2014 Jan 16 |
ISSN | 2211-1247 |
Keywords | Apoptosis, 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. |
DOI | 10.1016/j.celrep.2013.12.027 |
Alternate Journal | Cell Rep |
PubMed ID | 24388756 |
PubMed Central ID | PMC4100800 |
Grant List | U54-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.