QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Faculty of Medicine, University of Queensland, Queensland, Australia.
Mol Cancer Res. 2021 Jun;19(6):991-1004. doi: 10.1158/1541-7786.MCR-20-0839. Epub 2021 Mar 11.
Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the "main" cohort ( = 173; fresh-frozen samples), "validation" cohort ( = 48; formalin-fixed, paraffin-embedded samples) and a second "validation" cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in , and were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed , and as significantly mutated genes. and mutations occurred more commonly in lower anatomy melanomas and in the upper anatomy. , and were commonly affected by chromosomal copy loss, while , and were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. IMPLICATIONS: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg.
黏膜黑色素瘤是一种罕见的黑色素瘤亚型。迄今为止，尚未对来自多个研究的驱动事件异常和聚集频率进行全面系统的整理和统计分析。确定了使用全基因组、全外显子组、靶向基因面板或单个基因测序发表的研究。整理了这些研究的数据集，以总结突变、结构变异和拷贝数改变区域。将使用下一代测序的研究分为“主要”队列（=173；新鲜冷冻样本）、“验证”队列（=48；福尔马林固定、石蜡包埋样本）和第二个“验证”队列，该队列由 104 个使用靶向面板测序的肿瘤组成。总结了评估 、 和 中的突变，以评估热点突变。对主要队列变异数据的统计分析显示 、 和 是显著突变的基因。 和 突变更常见于下解剖学黑色素瘤和 在上解剖学。 、 和 常受到染色体拷贝数丢失的影响，而 、 和 常被扩增。进一步发生的频率较低的显著基因组改变表明，在肿瘤发生过程中，信号转导网络具有共同性，包括 MAPK、PI3K、Notch、Wnt/β-catenin、细胞周期、DNA 修复和端粒维持途径。这种分析确定了基因组异常，为特定途径可能被破坏的方式提供了一些见解。意义：我们的分析表明，黏膜黑色素瘤在几个生物学途径中具有多种基因组改变。直观描述：http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg。
