| Title | Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg M-L, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SYoung, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong Y-L, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS |
| Journal | Cell |
| Volume | 171 |
| Issue | 2 |
| Pagination | 481-494.e15 |
| Date Published | 2017 Oct 05 |
| ISSN | 1097-4172 |
| Keywords | Antineoplastic Agents, Cell Line, Tumor, Cells, Cultured, CRISPR-Cas Systems, Exome, Female, Gene Expression Profiling, Humans, Lymphoma, Large B-Cell, Diffuse, Male, Rituximab |
| Abstract | Diffuse large B cell lymphoma (DLBCL) is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Here, we performed an integrative analysis of whole-exome sequencing and transcriptome sequencing in a cohort of 1,001 DLBCL patients to comprehensively define the landscape of 150 genetic drivers of the disease. We characterized the functional impact of these genes using an unbiased CRISPR screen of DLBCL cell lines to define oncogenes that promote cell growth. A prognostic model comprising these genetic alterations outperformed current established methods: cell of origin, the International Prognostic Index comprising clinical variables, and dual MYC and BCL2 expression. These results comprehensively define the genetic drivers and their functional roles in DLBCL to identify new therapeutic opportunities in the disease. |
| DOI | 10.1016/j.cell.2017.09.027 |
| Alternate Journal | Cell |
| PubMed ID | 28985567 |
| PubMed Central ID | PMC5659841 |
| Grant List | R01 CA193655 / CA / NCI NIH HHS / United States T32 GM071340 / GM / NIGMS NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.