Journal Article

Distinct Molecular Landscape of Epstein-Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing

Wong, Shela Shu-Yan, Kwan, Johnny Sheung-Him, Mok, Tony Shu-Kam, Lung, Raymond Wai-Ming, Lo, Kwok-Wai, Ng, Calvin Sze-Hang, Tong, Joanna Hung-Man, Tin, Edith Ka-Yee, To, Ka-Fai, Cheung, Alvin Ho-Kwan, Chow, Chit, Chau, Shuk-Ling, Chung, Lau-Ying, Lau, Rainbow Wing-Hung

2020

Overview

Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein-Barr virus (EBV). The molecular basis underlying the disease remains unclear. We sought to study the molecular landscape by multiple approaches including whole genomic sequencing, capture-based targeted sequencing, fluorescent in situ hybridization and immunohistochemistry Tumor cells from 57 EBV-positive pulmonary LELCs were isolated by careful microdissection prior to genomic sequencing. Integrated analysis revealed a distinct genomic landscape of low TP53 mutation rate (11%), low incidence of known drivers in the RTK/RAS/RAF (11%) and PI3K/AKT/mTOR pathways (7%), but enriched for loss-of-function mutations in multiple negative regulators of the NF-KB pathway. High level programmed cell death ligand-1 (PD-L1) expression was shown with 47% and 79% of the cases showing positive PD-L1 immunoreactivity at >50% and >1% tumor proportion score, respectively. Subsets of the patients with actionable fibroblast growth factor receptor 3 (FGFR3) aberrations (4%) and mismatch repair deficiency (4%) were potentially eligible for precision medicine. Pulmonary LELC showed a distinct genomic landscape, different from major NSCLC subtypes but resembled that of EBV-associated nasopharyngeal carcinoma. Our work facilitated the understanding of molecular basis underlying pulmonary LELC to explore potential therapeutic options.

• Publisher: MDPI AG,MDPI
• Subject: 1-Phosphatidylinositol 3-kinase / Age / AKT protein / Apoptosis / Cancer therapies / Cell cycle / Cell death / Chromosomes / DNA sequencing / Epstein-Barr virus / Fibroblast growth factor receptor 3 / Fibroblast growth factor receptors / Fluorescence in situ hybridization / Gender / Genes / Genetic aspects / Genomes / Genomics / Health aspects / Histology / Immunohistochemistry / Infections / Lung cancer / Lung cancer, Non-small cell / Lung carcinoma / Lymphatic system / Medical prognosis / Metastases / Metastasis / Methods / Mismatch repair / Mutation / Mutation rates / Nasopharyngeal carcinoma / NF-κB protein / Non-small cell lung carcinoma / Nucleotide sequencing / p53 Protein / Patients / PD-L1 protein / Precision medicine / Raf protein / Small cell lung carcinoma / Survival analysis / TOR protein / Tumor cells