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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MDPI AG
2019-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/5/722 |
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| author | Kazuya Shinmura Hisami Kato Yuichi Kawanishi Katsuhiro Yoshimura Kazuo Tsuchiya Yoshiyuki Takahara Seiji Hosokawa Akikazu Kawase Kazuhito Funai Haruhiko Sugimura |
| author_facet | Kazuya Shinmura Hisami Kato Yuichi Kawanishi Katsuhiro Yoshimura Kazuo Tsuchiya Yoshiyuki Takahara Seiji Hosokawa Akikazu Kawase Kazuhito Funai Haruhiko Sugimura |
| author_sort | Kazuya Shinmura |
| collection | DOAJ |
| 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 <i>supF</i> 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. |
| first_indexed | 2024-03-12T11:17:44Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T11:17:44Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7df3d1e63d9447888fd7134f2cd7c20c2023-09-02T01:45:18ZengMDPI AGCancers2072-66942019-05-0111572210.3390/cancers11050722cancers11050722POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung AdenocarcinomaKazuya Shinmura0Hisami Kato1Yuichi Kawanishi2Katsuhiro Yoshimura3Kazuo Tsuchiya4Yoshiyuki Takahara5Seiji Hosokawa6Akikazu Kawase7Kazuhito Funai8Haruhiko Sugimura9Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanAdvanced Research Facilities and Services, Preeminent Medical Photonics Education and Research Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Surgery 1, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDepartment of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka 431-3192, JapanDNA 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 <i>supF</i> 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.https://www.mdpi.com/2072-6694/11/5/722lung adenocarcinomaPOLQ overexpressionPLK4 overexpressionsomatic mutation loadcentrosome amplificationtranslesion DNA synthesis |
| spellingShingle | Kazuya Shinmura Hisami Kato Yuichi Kawanishi Katsuhiro Yoshimura Kazuo Tsuchiya Yoshiyuki Takahara Seiji Hosokawa Akikazu Kawase Kazuhito Funai Haruhiko Sugimura POLQ Overexpression Is Associated with an Increased Somatic Mutation Load and PLK4 Overexpression in Lung Adenocarcinoma Cancers lung adenocarcinoma POLQ overexpression PLK4 overexpression somatic mutation load centrosome amplification translesion DNA synthesis |
| 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 | lung adenocarcinoma POLQ overexpression PLK4 overexpression somatic mutation load centrosome amplification translesion DNA synthesis |
| url | https://www.mdpi.com/2072-6694/11/5/722 |
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