Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

TitleGenetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.
Publication TypeJournal Article
Year of Publication2023
AuthorsThomas N, Dreval K, Gerhard DS, Hilton LK, Abramson JS, Ambinder RF, Barta S, Bartlett NL, Bethony J, Bhatia K, Bowen J, Bryan AC, Cesarman E, Casper C, Chadburn A, Cruz M, Dittmer DP, Dyer MA, Farinha P, Gastier-Foster JM, Gerrie AS, Grande BM, Greiner T, Griner NB, Gross TG, Harris NL, Irvin JD, Jaffe ES, Henry D, Huppi R, Leal FE, Lee MS, Martin JPaul, Martin M-R, Mbulaiteye SM, Mitsuyasu R, Morris V, Mullighan CG, Mungall AJ, Mungall K, Mutyaba I, Nokta M, Namirembe C, Noy A, Ogwang MD, Omoding A, Orem J, Ott G, Petrello H, Pittaluga S, Phelan JD, Ramos JCarlos, Ratner L, Reynolds SJ, Rubinstein PG, Sissolak G, Slack G, Soudi S, Swerdlow SH, Traverse-Glehen A, Wilson WH, Wong J, Yarchoan R, ZenKlusen JC, Marra MA, Staudt LM, Scott DW, Morin RD
Date Published2023 Feb 23
KeywordsAdult, Burkitt Lymphoma, Child, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Humans, Lymphoma, Large B-Cell, Diffuse, Mutation

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

Alternate JournalBlood
PubMed ID36201743
PubMed Central IDPMC10023728
Grant ListHHSN261201100007I / CA / NCI NIH HHS / United States
P01 CA019014 / CA / NCI NIH HHS / United States
75N91019D00024 / CA / NCI NIH HHS / United States
HHSN261201100063C / CA / NCI NIH HHS / United States
HHSN261200800001C / CA / NCI NIH HHS / United States
P30 CA021765 / CA / NCI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
R35 CA197695 / CA / NCI NIH HHS / United States
HHSN261201100007C / CA / NCI NIH HHS / United States
UM1 CA121947 / CA / NCI NIH HHS / United States
75N91020C00003 / CA / NCI NIH HHS / United States
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Amy Chadburn, M.D. Ethel Cesarman, M.D., Ph.D.

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