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Genomic alterations in thymoma—molecular pathogenesis?
Thymomas and thymic carcinomas (TCs) are neoplasms of thymic epithelial cells. Thymomas exhibit a low mutational burden and a few recurrently mutated genes. The most frequent missense mutation p.(Leu404His) affects the general transcription factor IIi (GTF2I) and is specific for thymic epithelial tu...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797814/ https://www.ncbi.nlm.nih.gov/pubmed/33447444 http://dx.doi.org/10.21037/jtd.2019.12.52 |
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author | Oberndorfer, Felicitas Müllauer, Leonhard |
author_facet | Oberndorfer, Felicitas Müllauer, Leonhard |
author_sort | Oberndorfer, Felicitas |
collection | PubMed |
description | Thymomas and thymic carcinomas (TCs) are neoplasms of thymic epithelial cells. Thymomas exhibit a low mutational burden and a few recurrently mutated genes. The most frequent missense mutation p.(Leu404His) affects the general transcription factor IIi (GTF2I) and is specific for thymic epithelial tumors (TETs). The clinically indolent types A and AB thymomas express the miRNA cluster C19MC. This miRNA cluster known to be the largest in the human genome, is—with expression otherwise restricted mostly to embryonal tissue—silenced in the more aggressive type B thymomas and TCs. Thymomas associated with the autoimmune disease myasthenia gravis (MG) exhibit more frequent gene copy number changes and an increased expression of proteins homologous to molecules that are targets for autoantibodies. TCs, however, display a higher mutational burden, with frequent mutations of TP53 and epigenetic regulatory genes and loss of CDKN2A. The knowledge of molecular alterations in TETs fosters the understanding of their pathogenesis and provides guidance for further studies that may lead to the development of targeted therapies. |
format | Online Article Text |
id | pubmed-7797814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-77978142021-01-13 Genomic alterations in thymoma—molecular pathogenesis? Oberndorfer, Felicitas Müllauer, Leonhard J Thorac Dis Review Article on Thymoma Thymomas and thymic carcinomas (TCs) are neoplasms of thymic epithelial cells. Thymomas exhibit a low mutational burden and a few recurrently mutated genes. The most frequent missense mutation p.(Leu404His) affects the general transcription factor IIi (GTF2I) and is specific for thymic epithelial tumors (TETs). The clinically indolent types A and AB thymomas express the miRNA cluster C19MC. This miRNA cluster known to be the largest in the human genome, is—with expression otherwise restricted mostly to embryonal tissue—silenced in the more aggressive type B thymomas and TCs. Thymomas associated with the autoimmune disease myasthenia gravis (MG) exhibit more frequent gene copy number changes and an increased expression of proteins homologous to molecules that are targets for autoantibodies. TCs, however, display a higher mutational burden, with frequent mutations of TP53 and epigenetic regulatory genes and loss of CDKN2A. The knowledge of molecular alterations in TETs fosters the understanding of their pathogenesis and provides guidance for further studies that may lead to the development of targeted therapies. AME Publishing Company 2020-12 /pmc/articles/PMC7797814/ /pubmed/33447444 http://dx.doi.org/10.21037/jtd.2019.12.52 Text en 2020 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Review Article on Thymoma Oberndorfer, Felicitas Müllauer, Leonhard Genomic alterations in thymoma—molecular pathogenesis? |
title | Genomic alterations in thymoma—molecular pathogenesis? |
title_full | Genomic alterations in thymoma—molecular pathogenesis? |
title_fullStr | Genomic alterations in thymoma—molecular pathogenesis? |
title_full_unstemmed | Genomic alterations in thymoma—molecular pathogenesis? |
title_short | Genomic alterations in thymoma—molecular pathogenesis? |
title_sort | genomic alterations in thymoma—molecular pathogenesis? |
topic | Review Article on Thymoma |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797814/ https://www.ncbi.nlm.nih.gov/pubmed/33447444 http://dx.doi.org/10.21037/jtd.2019.12.52 |
work_keys_str_mv | AT oberndorferfelicitas genomicalterationsinthymomamolecularpathogenesis AT mullauerleonhard genomicalterationsinthymomamolecularpathogenesis |