The genomic landscape of Epstein-Barr virus-associated pulmonary lymphoepithelioma-like carcinoma

• DOI: 10.1038/s41467-019-10902-w
• Publication Date: 2019-07-16T10:03:16Z
• Authors: Shaodong Hong; Dongbing Liu; Shuzhen Luo; Wenfeng Fang; Jianhua Zhan; Sha Fu; Yaxiong Zhang; Xuan Wu; Huaqiang Zhou; Xi Chen; Gang Chen; Zhonghan Zhang; Qiufan Zheng; Xiaobo Li; Jinghao Chen; Xingmin Liu; Mengyue Lei; Chen Ye; Jian Wang; Huanming Yang; Xun Xu; Shida Zhu; Yunpeng Yang; Yuanyuan Zhao; Ningning Zhou; Hongyun Zhao; Yan Huang; Lanjun Zhang; Kui Wu; Li Zhang
• Keywords: Adult; Male; 0301 basic medicine; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Lung Neoplasms; Science; Q; Carcinoma; DNA Mutational Analysis; Genomics; Middle Aged; Article; 3. Good health; 03 medical and health sciences; Humans; Female; Precision Medicine; Lung; Aged

AbstractPulmonary lymphoepithelioma-like carcinoma (LELC) is a rare and distinct subtype of primary lung cancer characterized by Epstein-Barr virus (EBV) infection. Herein, we reported the mutational landscape of pulmonary LELC using whole-exome sequencing, targeted deep sequencing and single-nucleotide polymorphism arrays. We identify a low degree of somatic mutation but widespread existence of copy number variations. We reveal predominant signature 2 mutations and frequent loss of type I interferon genes that are involved in the host-virus counteraction. Integrated analysis shows enrichment of genetic lesions affecting several critical pathways, including NF-κB, JAK/STAT, and cell cycle. Notably, multi-dimensional comparison unveils that pulmonary LELC resemble NPC but are clearly different from other lung cancers, natural killer/T-cell lymphoma or EBV-related gastric cancer in terms of genetic features. In all, our study illustrates a distinct genomic landscape of pulmonary LELC and provides a road map to facilitate genome-guided personalized treatment.