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POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma

DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs). In the present study, we examined whether abnormal POLQ expression may be involved in the pathogenesis of lung adenocarcinoma (LAC). Firs...

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Autores principales: Shinmura, Kazuya, Kato, Hisami, Kawanishi, Yuichi, Yoshimura, Katsuhiro, Tsuchiya, Kazuo, Takahara, Yoshiyuki, Hosokawa, Seiji, Kawase, Akikazu, Funai, Kazuhito, Sugimura, Haruhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562496/
https://www.ncbi.nlm.nih.gov/pubmed/31137743
http://dx.doi.org/10.3390/cancers11050722
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author Shinmura, Kazuya
Kato, Hisami
Kawanishi, Yuichi
Yoshimura, Katsuhiro
Tsuchiya, Kazuo
Takahara, Yoshiyuki
Hosokawa, Seiji
Kawase, Akikazu
Funai, Kazuhito
Sugimura, Haruhiko
author_facet Shinmura, Kazuya
Kato, Hisami
Kawanishi, Yuichi
Yoshimura, Katsuhiro
Tsuchiya, Kazuo
Takahara, Yoshiyuki
Hosokawa, Seiji
Kawase, Akikazu
Funai, Kazuhito
Sugimura, Haruhiko
author_sort Shinmura, Kazuya
collection PubMed
description DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs). In the present study, we examined whether abnormal POLQ expression may be involved in the pathogenesis of lung adenocarcinoma (LAC). First, we found overexpression of POLQ at both the mRNA and protein levels in LAC, using data from the Cancer Genome Atlas (TCGA) database and by immunohistochemical analysis of our LAC series. POLQ overexpression was associated with an advanced pathologic stage and an increased total number of somatic mutations in LAC. When H1299 human lung cancer cell clones overexpressing POLQ were established and examined, the clones showed resistance to a DSB-inducing chemical in the clonogenic assay and an increased frequency of mutations in the supF forward mutation assay. Further analysis revealed that POLQ overexpression was also positively correlated with Polo Like Kinase 4 (PLK4) overexpression in LAC, and that PLK4 overexpression in the POLQ-overexpressing H1299 cells induced centrosome amplification. Finally, analysis of the TCGA data revealed that POLQ overexpression was associated with an increased somatic mutation load and PLK4 overexpression in diverse human cancers; on the other hand, overexpressions of nine TLS polymerases other than POLQ were associated with an increased somatic mutation load at a much lower frequency. Thus, POLQ overexpression is associated with advanced pathologic stage, increased somatic mutation load, and PLK4 overexpression, the last inducing centrosome amplification, in LAC, suggesting that POLQ overexpression is involved in the pathogenesis of LAC.
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spelling pubmed-65624962019-06-17 POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma Shinmura, Kazuya Kato, Hisami Kawanishi, Yuichi Yoshimura, Katsuhiro Tsuchiya, Kazuo Takahara, Yoshiyuki Hosokawa, Seiji Kawase, Akikazu Funai, Kazuhito Sugimura, Haruhiko Cancers (Basel) Article DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs). In the present study, we examined whether abnormal POLQ expression may be involved in the pathogenesis of lung adenocarcinoma (LAC). First, we found overexpression of POLQ at both the mRNA and protein levels in LAC, using data from the Cancer Genome Atlas (TCGA) database and by immunohistochemical analysis of our LAC series. POLQ overexpression was associated with an advanced pathologic stage and an increased total number of somatic mutations in LAC. When H1299 human lung cancer cell clones overexpressing POLQ were established and examined, the clones showed resistance to a DSB-inducing chemical in the clonogenic assay and an increased frequency of mutations in the supF forward mutation assay. Further analysis revealed that POLQ overexpression was also positively correlated with Polo Like Kinase 4 (PLK4) overexpression in LAC, and that PLK4 overexpression in the POLQ-overexpressing H1299 cells induced centrosome amplification. Finally, analysis of the TCGA data revealed that POLQ overexpression was associated with an increased somatic mutation load and PLK4 overexpression in diverse human cancers; on the other hand, overexpressions of nine TLS polymerases other than POLQ were associated with an increased somatic mutation load at a much lower frequency. Thus, POLQ overexpression is associated with advanced pathologic stage, increased somatic mutation load, and PLK4 overexpression, the last inducing centrosome amplification, in LAC, suggesting that POLQ overexpression is involved in the pathogenesis of LAC. MDPI 2019-05-24 /pmc/articles/PMC6562496/ /pubmed/31137743 http://dx.doi.org/10.3390/cancers11050722 Text en © 2019 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
Shinmura, Kazuya
Kato, Hisami
Kawanishi, Yuichi
Yoshimura, Katsuhiro
Tsuchiya, Kazuo
Takahara, Yoshiyuki
Hosokawa, Seiji
Kawase, Akikazu
Funai, Kazuhito
Sugimura, Haruhiko
POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title_full POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title_fullStr POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title_full_unstemmed POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title_short POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma
title_sort polq overexpression is associated with an increased somatic mutation load and plk4 overexpression in lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562496/
https://www.ncbi.nlm.nih.gov/pubmed/31137743
http://dx.doi.org/10.3390/cancers11050722
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