Department of Medical Oncology, Sun Yat-sen University Cancer Center, 510060, Guangzhou, China.
State Key Laboratory of Oncology in South China, 510060, Guangzhou, China.
Nat Commun. 2019 Jul 16;10(1):3108. doi: 10.1038/s41467-019-10902-w.
Pulmonary 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.
肺淋巴上皮瘤样癌（LELC）是一种罕见且独特的原发性肺癌亚型，其特征是 Epstein-Barr 病毒（EBV）感染。在此，我们通过全外显子组测序、靶向深度测序和单核苷酸多态性芯片分析了肺 LELC 的突变全景。我们发现体细胞突变程度较低，但存在广泛的拷贝数变异。我们揭示了主要的 signature 2 突变和频繁的Ⅰ型干扰素基因缺失，这些基因参与了宿主-病毒的相互作用。综合分析显示，遗传病变富集影响了多个关键通路，包括 NF-κB、JAK/STAT 和细胞周期。值得注意的是，多维比较表明，肺 LELC 与 NPC 相似，但在遗传特征上与其他肺癌、自然杀伤/T 细胞淋巴瘤或 EBV 相关胃癌明显不同。总之，我们的研究阐明了肺 LELC 的独特基因组景观，并提供了一个路线图，以促进基于基因组的个性化治疗。
