Next-generation sequencing in advanced Chinese melanoma reveals therapeutic targets and prognostic biomarkers for immunotherapy.
Next-generation sequencing in advanced Chinese melanoma reveals therapeutic targets and prognostic biomarkers for immunotherapy.
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DOI：
10.1038/s41598-022-13391-y
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发表时间：
2022-06-10
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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作者：
有限的研究询问了中国黑色素瘤的基因组格局，其中肢端黑色素瘤和粘膜黑色素瘤是主要的。本研究对81例中国人黑色素瘤患者(肢端黑色素瘤15例，粘膜黑色素瘤25例，皮肤黑色素瘤41例)进行了回顾性分析。通过对涉及248个基因的1114个突变的鉴定，我们总结出突变谱在不同亚型之间存在显著差异。肢端黑色素瘤和粘膜黑色素瘤CNV明显增多。MYC扩增是最常见的CNV之一，粘膜黑色素瘤中其他常见CNV包括NBN和KDR，它们与黑色素瘤患者的生存不良有关。包括皮肤黑色素瘤在内的三组TMB普遍较低，中位数仅为5.1MUT/Mb。此外，在所有三种亚型中都检测到了DNA损伤修复途径的50%以上的变异，其中大部分是HRD相关基因。HRD相关基因改变的患者免疫治疗后生存时间较长。本研究揭示了中国人晚期黑色素瘤的分子特征，并提出DDR通路的高变异率可作为免疫治疗的生物标志物，为不同类型的中国人黑色素瘤的治疗提供靶点和指导临床决策。
Limited studies have interrogated the genomic landscape of Chinese melanoma in which acral and mucosal melanoma are the mainstay. In this study, we carried out a retrospective analysis on 81 Chinese melanoma patients (15 acral, 25 mucosal and 41 cutaneous melanoma). With the identification of 1114 mutations spanning 248 genes, we summarized that the mutation spectrum varied significantly by subtypes. Acral melanoma and mucosal melanoma had significantly more CNVs. MYC amplification was one of the most commonly detected CNVs, other frequent CNVs in mucosal melanoma included NBN and KDR, which were associated with the poor survival of melanoma patients. A generally low TMB, with a median of only 5.1 mut/Mb, was observed in three groups including cutaneous melanoma. Additionally, over 50% variants in DNA damage repair pathway were detected in all three subtypes, most of which were HRD related genes. Patients with alterations of HRD related genes had a longer survival time after immunotherapy. This study revealed a molecular profiling of Chinese patients with advanced melanoma, and proposed the high variant rate in DDR pathway as a biomarker of immunotherapy, which might provide therapeutic targets and guidance in making clinical decision for different Chinese melanoma.
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DOI：
10.1158/1078-0432.ccr-20-4189
发表时间：
2021-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Shoushtari AN;Chatila WK;Arora A;Sanchez-Vega F;Kantheti HS;Rojas Zamalloa JA;Krieger P;Callahan MK;Betof Warner A;Postow MA;Momtaz P;Nair S;Ariyan CE;Barker CA;Brady MS;Coit DG;Rosen N;Chapman PB;Busam KJ;Solit DB;Panageas KS;Wolchok JD;Schultz N
通讯作者：
Schultz N
中国黑色素瘤患者中 BRAF V600E 突变的患病率：432 例队列中 BRAF 和 NRAS 突变的大规模分析
影响因子：
8.4
作者：
Si, Lu;Kong, Yan;Guo, Jun
通讯作者：
Guo, Jun
中国黑色素瘤患者 KIT 畸变的大规模分析
影响因子：
11.5
作者：
Kong, Yan;Si, Lu;Guo, Jun
通讯作者：
Guo, Jun
影响因子：
45.3
作者：
Konstantinopoulos, Panagiotis A.;Spentzos, Dimitrios;Cannistra, Stephen A.
通讯作者：
Cannistra, Stephen A.
影响因子：
11.4
作者：
Kfoury, Alain;Armaro, Marzia;Radtke, Freddy
通讯作者：
Radtke, Freddy