{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:47:17Z","timestamp":1787784437043,"version":"build-2784847793"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Chinese University of Hong Kong","award":["Vice-Chancellor\u2019s One-off Discretionary Fund"],"award-info":[{"award-number":["Vice-Chancellor\u2019s One-off Discretionary Fund"]}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["T12\u2010401\/13\u2010R; C4001-18GF; C7027-16G; 14117316"],"award-info":[{"award-number":["T12\u2010401\/13\u2010R; C4001-18GF; C7027-16G; 14117316"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Pulmonary lymphoepithelioma-like carcinoma (LELC) is a subtype of non-small cell lung cancer (NSCLC) characterized by marked lymphocytic infiltration and association with Epstein\u2013Barr 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-\u03baB 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 \u226550% and \u22651% 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.<\/jats:p>","DOI":"10.3390\/cancers12082065","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T04:39:50Z","timestamp":1595824790000},"page":"2065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Distinct Molecular Landscape of Epstein\u2013Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-5767","authenticated-orcid":false,"given":"Shuk-Ling","family":"Chau","sequence":"first","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna Hung-Man","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chit","family":"Chow","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny Sheung-Him","family":"Kwan","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-7429","authenticated-orcid":false,"given":"Raymond Wai-Ming","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lau-Ying","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith Ka-Yee","family":"Tin","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-352X","authenticated-orcid":false,"given":"Shela Shu-Yan","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin Ho-Kwan","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainbow Wing-Hung","family":"Lau","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Calvin Sze-Hang","family":"Ng","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony Shu-Kam","family":"Mok","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Wai","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Fai","family":"To","sequence":"additional","affiliation":[{"name":"Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China"},{"name":"Sir Y.K. Pao Cancer Center, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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