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致癌性改变揭示了黑色素瘤治疗中精准肿瘤学的关键策略。

Oncogenic alterations reveal key strategies for precision oncology in melanoma treatment.

作者信息

Sun Wei, Zhao Fang, Hu Tu, Wu Zhiqiang, Xu Yu, Dong Yan, Zheng Biqiang, Wang Chunmeng, Yan Wangjun, Zhu Xiaoli, Wu Jian, McKay Michael J, Arozarena Imanol, Alos Llucia, Teixido Cristina, Chen Yong

机构信息

Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Ann Transl Med. 2022 Nov;10(22):1246. doi: 10.21037/atm-22-5346.

Abstract

BACKGROUND

Molecular profiling with next-generation sequencing (NGS) has been applied in multiple solid tumors, including melanomas, to identify potential drug targets. However, the association between clinical outcomes and the molecular alterations has not yet been fully clarified.

METHODS

A total of 108 patients with melanoma were included in this study, 95 of whom had both sequencing data and clinical outcomes were collected. We analyzed the genetic alterations of 108 malignant melanoma patients using the OncoCare panel, which covers 559 genes.

RESULTS

A model was also established to predict side effects through a combination analysis of clinical data and somatic variants, yielding an area under the receiver operating characteristic curve (AUROC) score of 0.8. We also identified epidermal growth factor receptor (EGFR) mutation was excellent predictor for progression-free survival (PFS) for patient who received immunotherapy (log-rank P=0.01), while tumor mutation burden (TMB) was found to not be significantly associated with PFS (log-rank P=0.87). Combining clinical features with genetic analysis, we found that patients carrying both DNA POLD1/ALOX12B or POLD1/PTPRT mutations had a significantly lower survival rate.

CONCLUSIONS

Overall, these results demonstrate the benefits of applying NGS clinical panels and shed light on future directions of personalized therapeutics for the treatment of melanoma.

摘要

背景

采用下一代测序(NGS)进行分子谱分析已应用于包括黑色素瘤在内的多种实体瘤,以识别潜在的药物靶点。然而,临床结果与分子改变之间的关联尚未完全阐明。

方法

本研究共纳入108例黑色素瘤患者,其中95例同时收集了测序数据和临床结果。我们使用覆盖559个基因的OncoCare检测板分析了108例恶性黑色素瘤患者的基因改变。

结果

还通过临床数据和体细胞变异的联合分析建立了一个预测副作用的模型,受试者操作特征曲线(AUROC)下面积得分为0.8。我们还发现,表皮生长因子受体(EGFR)突变是接受免疫治疗患者无进展生存期(PFS)的良好预测指标(对数秩检验P=0.01),而肿瘤突变负荷(TMB)与PFS无显著相关性(对数秩检验P=0.87)。结合临床特征与基因分析,我们发现同时携带DNA聚合酶δ1(POLD1)/花生四烯酸12-脂氧合酶(ALOX12B)或POLD1/蛋白酪氨酸磷酸酶受体T(PTPRT)突变的患者生存率显著较低。

结论

总体而言,这些结果证明了应用NGS临床检测板的益处,并为黑色素瘤个性化治疗的未来方向提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e94/9761125/3d4a72049d9e/atm-10-22-1246-f1.jpg

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