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

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...

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Autores principales: Chau, Shuk-Ling, Tong, Joanna Hung-Man, Chow, Chit, Kwan, Johnny Sheung-Him, Lung, Raymond Wai-Ming, Chung, Lau-Ying, Tin, Edith Ka-Yee, Wong, Shela Shu-Yan, Cheung, Alvin Ho-Kwan, Lau, Rainbow Wing-Hung, Ng, Calvin Sze-Hang, Mok, Tony Shu-Kam, Lo, Kwok-Wai, To, Ka-Fai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463519/
https://www.ncbi.nlm.nih.gov/pubmed/32726920
http://dx.doi.org/10.3390/cancers12082065
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author Chau, Shuk-Ling
Tong, Joanna Hung-Man
Chow, Chit
Kwan, Johnny Sheung-Him
Lung, Raymond Wai-Ming
Chung, Lau-Ying
Tin, Edith Ka-Yee
Wong, Shela Shu-Yan
Cheung, Alvin Ho-Kwan
Lau, Rainbow Wing-Hung
Ng, Calvin Sze-Hang
Mok, Tony Shu-Kam
Lo, Kwok-Wai
To, Ka-Fai
author_facet Chau, Shuk-Ling
Tong, Joanna Hung-Man
Chow, Chit
Kwan, Johnny Sheung-Him
Lung, Raymond Wai-Ming
Chung, Lau-Ying
Tin, Edith Ka-Yee
Wong, Shela Shu-Yan
Cheung, Alvin Ho-Kwan
Lau, Rainbow Wing-Hung
Ng, Calvin Sze-Hang
Mok, Tony Shu-Kam
Lo, Kwok-Wai
To, Ka-Fai
author_sort Chau, Shuk-Ling
collection PubMed
description 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-κB 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.
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spelling pubmed-74635192020-09-04 Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing Chau, Shuk-Ling Tong, Joanna Hung-Man Chow, Chit Kwan, Johnny Sheung-Him Lung, Raymond Wai-Ming Chung, Lau-Ying Tin, Edith Ka-Yee Wong, Shela Shu-Yan Cheung, Alvin Ho-Kwan Lau, Rainbow Wing-Hung Ng, Calvin Sze-Hang Mok, Tony Shu-Kam Lo, Kwok-Wai To, Ka-Fai Cancers (Basel) Article 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-κB 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. MDPI 2020-07-27 /pmc/articles/PMC7463519/ /pubmed/32726920 http://dx.doi.org/10.3390/cancers12082065 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chau, Shuk-Ling
Tong, Joanna Hung-Man
Chow, Chit
Kwan, Johnny Sheung-Him
Lung, Raymond Wai-Ming
Chung, Lau-Ying
Tin, Edith Ka-Yee
Wong, Shela Shu-Yan
Cheung, Alvin Ho-Kwan
Lau, Rainbow Wing-Hung
Ng, Calvin Sze-Hang
Mok, Tony Shu-Kam
Lo, Kwok-Wai
To, Ka-Fai
Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title_full Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title_fullStr Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title_full_unstemmed Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title_short Distinct Molecular Landscape of Epstein–Barr Virus Associated Pulmonary Lymphoepithelioma-Like Carcinoma Revealed by Genomic Sequencing
title_sort distinct molecular landscape of epstein–barr virus associated pulmonary lymphoepithelioma-like carcinoma revealed by genomic sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463519/
https://www.ncbi.nlm.nih.gov/pubmed/32726920
http://dx.doi.org/10.3390/cancers12082065
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