Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Song Joo Y, Perry Anamarija M, Herrera Alex F, Chen Lu, Skrabek Pamela, Nasr Michel R, Ottesen Rebecca A, Nikowitz Janet, Bedell Victoria, Murata-Collins Joyce, Li Yuping, McCarthy Christine, Pillai Raju, Wang Jinhui, Wu Xiwei, Zain Jasmine, Popplewell Leslie, Kwak Larry W, Nademanee Auayporn P, Niland Joyce C, Scott David W, Gong Qiang, Chan Wing C, Weisenburger Dennis D
Аннотация
PURPOSE: We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).
EXPERIMENTAL DESIGN: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes.
RESULTS: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts.
CONCLUSIONS: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.
EXPERIMENTAL DESIGN: The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes.
RESULTS: We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts.
CONCLUSIONS: We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.
Предметные рубрики MeSH
Antineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCyclophosphamideDoxorubicinFemaleFollow-Up StudiesGene Expression ProfilingGerminal CenterHumansLymphoma, Large B-Cell, DiffuseMaleMiddle AgedMutationPrednisonePrognosisRetrospective StudiesRituximabSurvival RateTranslocation, GeneticTumor Suppressor Protein p53Vincristine