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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7463519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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