TP53 and OSBPL10 alterations in diffuse large B-cell lymphoma: prognostic markers identified via exome analysis of cases with extreme prognosis.
TP53 and OSBPL10 alterations in diffuse large B-cell lymphoma: prognostic markers identified via exome analysis of cases with extreme prognosis.
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DOI：
10.18632/oncotarget.24656
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发表时间：
2018-04-13
期刊：
影响因子：
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通讯作者：
Takeuchi K
中科院分区：
文献类型：
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作者：
Dobashi A;Togashi Y;Tanaka N;Yokoyama M;Tsuyama N;Baba S;Mori S;Hatake K;Yamaguchi T;Noda T;Takeuchi K
弥漫性大B细胞淋巴瘤（DLBCL）是最常见的淋巴瘤亚型，具有生物学和临床异质性。在难治性病例中，挽救治疗的完全缓解/完全缓解未确认率仍然较低。我们在一个包括26例预后良好和9例预后不良病例的发现队列中进行了DLBCL的全外显子组测序。在确定候选基因后，在DLBCL验证队列中的85个个体中检查了突变。在发现队列中，预后不良组中的5名患者同时携带TP 53突变和17 p缺失。在预后良好组的9例患者中，OSBPL 10中发现了16种突变，但在预后不良组中没有发现突变。在验证队列中，只有当两种畸变共存时，TP 53突变和TP 53缺失才被证实是总生存期（OS）（P = 0.016）和无进展生存期（PFS）（P = 0.023）的不良预后因素。OSBPL 10突变被验证为良好OS（P = 0.037）和PFS（P = 0.041）的预后标志物。当患者被分为三组时，OS和PFS的显著差异被观察到-OSBPL 10突变（最佳预后），TP 53突变和TP 53缺失共存（最差预后），以及其他。在这项研究中，TP 53突变和17 p/TP 53缺失的存在，而不是个别变异，与利妥昔单抗，环磷酰胺，多柔比星，长春新碱和泼尼松（R-CHOP）或类似方案治疗后的DLBCL患者预后不良相关。我们还将OSBPL 10突变确定为R-CHOP时代预后良好患者的标志物。
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype characterized by both biological and clinical heterogeneity. In refractory cases, complete response/complete response unconfirmed rates in salvage therapy remain low. We performed whole-exome sequencing of DLBCL in a discovery cohort comprising 26 good and nine poor prognosis cases. After candidate genes were identified, prognoses were examined in 85 individuals in the DLBCL validation cohort. In the discovery cohort, five patients in the poor prognosis group harbored both a TP53 mutation and 17p deletion. Sixteen mutations were identified in OSBPL10 in nine patients in the good prognosis group, but none in the poor prognosis group. In the validation cohort, TP53 mutations and TP53 deletions were confirmed to be poor prognostic factors for overall survival (OS) (P = 0.016) and progression-free survival (PFS) (P = 0.023) only when both aberrations co-existed. OSBPL10 mutations were validated as prognostic markers for excellent OS (P = 0.037) and PFS (P = 0.041). Significant differences in OS and PFS were observed when patients were stratified into three groups—OSBPL10 mutation (best prognosis), the coexistence of both TP53 mutation and TP53 deletion (poorest prognosis), and others. In this study, the presence of both TP53 mutation and 17p/TP53 deletion, but not the individual variants, was associated with poor prognosis in DLBCL patients after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or similar regimens. We also identified OSBPL10 mutation as a marker for patients with excellent prognosis in the R-CHOP era.