Department of Surgical Oncology, Fox Chase Cancer Center.
Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
Melanoma Res. 2022 Apr 1;32(2):112-119. doi: 10.1097/CMR.0000000000000808.
Tumor mutational burden (TMB) has recently been identified as a biomarker of response to immune checkpoint inhibitors in many cancers, including melanoma. Co-assessment of TMB with inflammatory markers and genetic mutations may better predict disease outcomes. The goal of this study was to evaluate the potential for TMB and somatic mutations in combination to predict the recurrence of disease in advanced melanoma. A retrospective review of 85 patients with stage III or IV melanoma whose tumors were analyzed by next-generation sequencing was conducted. Fisher's exact test was used to assess differences in TMB category by somatic mutation status as well as recurrence locations. Kaplan-Meier estimates and Cox-proportional regression model were used for survival analyses. The most frequently detected mutations were TERT (32.9%), CDKN2A (28.2%), KMT2 (25.9%), BRAF V600E (24.7%), and NRAS (24.7%). Patients with TMB-L + BRAFWT status were more likely to have a recurrence [hazard ratio (HR), 3.43; confidence interval (CI), 1.29-9.15; P = 0.01] compared to TMB-H + BRAF WT. Patients with TMB-L + NRASmut were more likely to have a recurrence (HR, 5.29; 95% CI, 1.44-19.45; P = 0.01) compared to TMB-H + NRAS WT. TMB-L tumors were associated with local (P = 0.029) and in-transit (P = 0.004) recurrences. Analysis of TMB alone may be insufficient in understanding the relationship between melanoma's molecular profile and the body's immune system. Classification into BRAFmut, NRASmut, and tumor mutational load groups may aid in identifying patients who are more likely to have disease recurrence in advanced melanoma.
肿瘤突变负担 (TMB) 最近已被确定为多种癌症（包括黑色素瘤）对免疫检查点抑制剂反应的生物标志物。TMB 与炎症标志物和遗传突变的共同评估可能更好地预测疾病结果。本研究的目的是评估 TMB 与体细胞突变相结合预测晚期黑色素瘤疾病复发的潜力。对 85 名 III 期或 IV 期黑色素瘤患者进行了回顾性研究，这些患者的肿瘤均通过下一代测序进行了分析。Fisher 确切检验用于评估体细胞突变状态和复发部位的 TMB 类别差异。Kaplan-Meier 估计和 Cox 比例风险回归模型用于生存分析。最常见的突变是 TERT（32.9%）、CDKN2A（28.2%）、KMT2（25.9%）、BRAF V600E（24.7%）和 NRAS（24.7%）。与 TMB-H + BRAF WT 相比，TMB-L + BRAFWT 状态的患者更有可能出现复发[风险比（HR），3.43；置信区间（CI），1.29-9.15；P = 0.01]。与 TMB-H + NRAS WT 相比，TMB-L + NRASmut 患者更有可能出现复发（HR，5.29；95%CI，1.44-19.45；P = 0.01）。TMB-L 肿瘤与局部（P = 0.029）和经皮转移（P = 0.004）复发相关。单独分析 TMB 可能不足以了解黑色素瘤分子谱与机体免疫系统之间的关系。BRAFmut、NRASmut 和肿瘤突变负荷组的分类可能有助于识别晚期黑色素瘤中更有可能出现疾病复发的患者。
