EB病毒相關鼻咽癌的基因組圖譜

編譯：腫瘤資訊來源：腫瘤資訊專家介紹

羅國偉教授

香港中文大學解剖和細胞病理學院

華南腫瘤學國家重點實驗室

羅國偉教授致力於鼻咽癌分子機制的研究，他成功描繪了鼻咽癌發生過程中的早期事件，並確定了這一EBV相關疾病複發相關的遺傳和表觀遺傳學異常。他在本次大會上的彙報主要展示了其應用二代測序的方法系統闡述鼻咽癌基因組特徵的一項近期研究。

該研究納入了111例經過顯微切割的EBV相關的鼻咽癌患者，包括CYLD, TRAF3, 和 NFKBIA在內的 NF-kB 信號通路多項負性調節因子的異常在41%鼻咽癌患者中被檢測到，功能分析提示CYLD 突變是鼻咽癌惡性進展的重要驅動基因。研究進一步揭示，EB病毒編碼的LMP1蛋白可導致鼻咽癌NF-kB信號通路的持續激活，LMP1 過表達和體細胞NF-kB異常改變是互斥的分子事件，提示LMP1 過表達和體細胞NF-kB異常改變均將導致鼻咽癌惡性進展過程中NF-kB信號通路的激活。

英文原文

The Genomic Landscape of EBV-associated Nasopharyngeal Carcinoma

Kwok-Wai Lo

The Chinese University of Hong Kong

Department of Anatomical & Cellular Pathology

State Key Laboratory in Oncology in South China

Prof KW Lo』s long term research interest is to unveil the molecular basis of nasopharyngeal carcinoma (NPC). He has successfully delineated the early events in NPC tumorigenesis and determined multiple recurrent genetic and epigenetic abnormalities in this EBV-associated cancer. Recently, he has systematically characterized the NPC genome by next-generation sequencing approaches. Whole-exome sequencing (WES) was performed on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. The study identified enrichment for genomic aberrations of multiple negative regulators of the NF-kB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-kB signalling, and they observed mutual exclusivity among tumours with somatic NF-kB pathway aberrations and LMP1-overexpression, suggesting that NF-kB activation is selected for by both somatic and viral events during NPC pathogenesis.

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