Department of Chemotherapy, Guangxi Medical University Affiliated Tumor Hospital, Nanning, China.
Cancer Med. 2022 Mar;11(5):1281-1291. doi: 10.1002/cam4.4550. Epub 2022 Feb 1.
There are over a 100 driver gene mutations in patients with diffuse large B-cell lymphoma (DLBCL), but their clinical significance remains unclear. Here, we first analyzed the DLBCL dataset from the UK-based Haematological Malignancy Research Network. Patients were divided into high- and low-risk groups based on whether lymphoma progressed within 24 months. Genes showing significantly different frequencies between groups were selected. Survival data for patients with the selected mutant genes were analyzed. The results were validated using two other large databases to evaluate the relationship between the selected mutant genes and prognosis. The mutation frequencies of 11 genes (MYD88[L265P], SGK1, MPEG1, TP53, SPEN, NOTCH1, ETV6, TNFRSF14, MGA, CIITA, and PIM1) significantly differed between the high- and low-risk groups. The relationships between these mutant genes and patient survival were analyzed. Patients who harbored SGK1 (serum and glucocorticoid-inducible kinase 1) mutations exhibited the best prognosis. Most patients with SGK1 mutation are germinal center B-cell (GCB) subtype. Among patients with GCB DLBCL, those harboring SGK1 mutations exhibited better prognosis than those without SGK1 mutations. Most SGK1 mutations were single-base substitutions, primarily scattered throughout the catalytic domain-encoding region. Multiple SGK1 mutations were identified in a single patient. Thus, SGK1 mutations are a marker of good prognosis for DLBCL and occur predominantly in the GCB subtype of DLBCL. SGK1 mutation status can further stratify patients with GCB DLBCL into different prognostic subgroups.
在弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者中，存在超过 100 种驱动基因突变，但它们的临床意义仍不清楚。在这里，我们首先分析了来自英国血液恶性肿瘤研究网络的 DLBCL 数据集。根据淋巴瘤是否在 24 个月内进展，将患者分为高危组和低危组。选择组间频率差异显著的基因。分析了具有所选突变基因的患者的生存数据。使用另外两个大型数据库验证了结果，以评估所选突变基因与预后之间的关系。11 个基因（MYD88[L265P]、SGK1、MPEG1、TP53、SPEN、NOTCH1、ETV6、TNFRSF14、MGA、CIITA 和 PIM1）的突变频率在高危组和低危组之间差异显著。分析了这些突变基因与患者生存之间的关系。携带 SGK1（血清和糖皮质激素诱导激酶 1）突变的患者预后最佳。大多数携带 SGK1 突变的患者为生发中心 B 细胞（GCB）亚型。在 GCB DLBCL 患者中，携带 SGK1 突变的患者比未携带 SGK1 突变的患者预后更好。大多数 SGK1 突变是单碱基取代，主要散布在催化结构域编码区。在单个患者中鉴定出多个 SGK1 突变。因此，SGK1 突变是 DLBCL 预后良好的标志物，主要发生在 DLBCL 的 GCB 亚型中。SGK1 突变状态可以进一步将 GCB DLBCL 患者分为不同的预后亚组。
