文章：

利用AACR项目GENIE数据库对鼻咽癌进行分子特征分析

Molecular Profiling of Nasopharyngeal Carcinoma Using the AACR Project GENIE Repository

原文发布日期：1 May 2025

DOI: 10.3390/cancers17091544

类型: Article

开放获取: 是

英文摘要：

Background: Nasopharyngeal carcinoma (NPC) is a rare head and neck cancer arising from the mucosal lining of the nasopharynx, for which systemic therapeutic options remain scarce, reflecting the limited characterization of its genomic profile. This study utilized a large patient-level genomic repository to characterize genetic alterations, identify potential therapeutic targets, and improve disease modeling in NPC. Methods: A retrospective analysis of NPC samples was conducted using the AACR Project GENIE database. Targeted sequencing data were analyzed for recurrent somatic mutations, tumor mutational burden, and chromosomal copy number variations, with significance set atp< 0.05. Results: Frequent mutations were identified inKMT2D(20%),TP53(16%),CYLD(9.6%),NFKBIA(6.4%), andPIK3CA(5.6%), implicating the p53, NF-κB, and PI3K pathways in NPC development. Notably, significantly distinct mutational profiles were observed based on both sex and race, with female patients exhibiting higher frequencies ofPIK3C2G,ETV6, andCDKN1Bmutations and non-Asian patients showing enrichment inKDM5A,CCND2, andTP53mutations. Conclusions: This study presents a detailed genomic profile of NPC, identifying key mutations within established cancer-associated pathways. The identification of frequently mutated pathways (p53, NF-κB, and PI3K) suggests potential targets for novel therapies. Furthermore, distinct mutational landscapes in female and Asian NPC patients offer possibilities for precision therapeutic interventions.

摘要翻译： 

背景：鼻咽癌是一种罕见的头颈部恶性肿瘤，起源于鼻咽部黏膜上皮层，其全身性治疗方案仍然有限，这反映出对其基因组特征的认知尚不充分。本研究利用大规模患者基因组数据库，系统描绘鼻咽癌的遗传变异图谱，识别潜在治疗靶点，并优化疾病模型构建。方法：基于美国癌症研究协会GENIE项目数据库，对鼻咽癌样本进行回顾性分析。通过靶向测序数据分析体细胞高频突变、肿瘤突变负荷及染色体拷贝数变异，显著性阈值设定为p<0.05。结果：研究发现KMT2D（20%）、TP53（16%）、CYLD（9.6%）、NFKBIA（6.4%）和PIK3CA（5.6%）基因存在高频突变，提示p53、NF-κB和PI3K信号通路参与鼻咽癌发生发展。值得注意的是，不同性别和种族患者呈现显著差异的突变谱：女性患者PIK3C2G、ETV6和CDKN1B突变频率更高，而非亚洲患者则表现出KDM5A、CCND2和TP53突变的富集。结论：本研究系统阐明了鼻咽癌的基因组特征，明确了关键癌症相关通路的核心突变。p53、NF-κB和PI3K通路的频繁突变提示其可作为新型治疗的潜在靶点。此外，女性和亚洲鼻咽癌患者独特的突变图谱为精准治疗干预提供了新方向。

原文链接：

Molecular Profiling of Nasopharyngeal Carcinoma Using the AACR Project GENIE Repository