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

ABSTRACT: 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-?B, 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.

SUBMITTER: Hong S

PROVIDER: S-EPMC6635366 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Hong Shaodong S Liu Dongbing D Luo Shuzhen S Fang Wenfeng W Zhan Jianhua J Fu Sha S Zhang Yaxiong Y Wu Xuan X Zhou Huaqiang H Chen Xi X Chen Gang G Zhang Zhonghan Z Zheng Qiufan Q Li Xiaobo X Chen Jinghao J Liu Xingmin X Lei Mengyue M Ye Chen C Wang Jian J Yang Huanming H Xu Xun X Zhu Shida S Yang Yunpeng Y Zhao Yuanyuan Y Zhou Ningning N Zhao Hongyun H Huang Yan Y Zhang Lanjun L Wu Kui K Zhang Li L

Nature communications 20190716 1

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 ge ...[more]

PMID: 31311932

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Project description:Purpose: To investigate the predictive values of plasma Epstein-Barr Virus (EBV)- deoxyribonucleic acid (DNA) copy number on disease progression and survival in stage I-III pulmonary lymphoepithelioma-like carcinoma (LELC). Patients and Methods: Patients with pathologically confirmed, initially diagnosed or locally recurrent stage I-III pulmonary LELC, who received locally radical treatment and had plasma EBV-DNA results, were retrospectively reviewed. Risk factors of progression-free survival (PFS) and overall survival (OS) were assessed, including the predictive value of pre- and post-treatment EBV-DNA levels. The EBV-DNA change during follow-up was analyzed to determine its association with tumor progression and survival. Results: A total of 102 patients were included in analysis. Eighty-eight patients had initially-diagnosed and 14 had locally recurrent disease. There were 33 patients treated with radical surgery, 55 with definite radiotherapy and 14 with both. EBV-DNA was tested pre-treatment (N = 66), post-treatment (N = 93) and/or during follow-up (N = 58). Forty-one patients had complete EBV-DNA results of all three time points. The overall 2-year PFS and OS were 66.3 and 96.0%, respectively. Pre-treatment EBV-DNA copy number > 10,000 copies/mL was a risk factor of PFS (2-year PFS, > 10,000 vs. ? 10,000 copies/mL, 37.2 vs. 75.1%, p = 0.007). Positive post-treatment EBV-DNA also indicated a worse PFS in univariable (2-year PFS, > 0 vs. 0 copy/mL, 25.6 vs. 76.8%, p < 0.001) and multivariable analysis (HR = 3.44, 95% CI, 1.52-7.78; p = 0.003). In the follow-up set, an increasing EBV-DNA exceeding 1,000 copies/mL strongly predicted disease progression within 3 months, with a specificity of 97.5% (95% CI: 86.8-99.6%) and was associated with impaired OS (2-year OS, > 1,000 vs. ? 1,000 copies/mL, 72.9 vs. 100%, p < 0.001). Conclusions: Regular testing of EBV-DNA is suggested for pulmonary LELC to predict disease progression. If EBV-DNA copy number was increasing and beyond 1,000 copies/mL during follow-up, intensive radiologic evaluations are recommended.

Dataset Information

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

Publications

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

Similar Datasets

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