The spectrum of TP53 mutations in Rwandan patients with gastric cancer
Abstract Background Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Genes and Environment |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41021-024-00302-y |
| _version_ | 1797219635543670784 |
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| author | Augustin Nzitakera Jean Bosco Surwumwe Ella Larissa Ndoricyimpaye Schifra Uwamungu Delphine Uwamariya Felix Manirakiza Marie Claire Ndayisaba Gervais Ntakirutimana Benoit Seminega Vincent Dusabejambo Eric Rutaganda Placide Kamali François Ngabonziza Rei Ishikawa Belson Rugwizangoga Yuji Iwashita Hidetaka Yamada Kimio Yoshimura Haruhiko Sugimura Kazuya Shinmura |
| author_facet | Augustin Nzitakera Jean Bosco Surwumwe Ella Larissa Ndoricyimpaye Schifra Uwamungu Delphine Uwamariya Felix Manirakiza Marie Claire Ndayisaba Gervais Ntakirutimana Benoit Seminega Vincent Dusabejambo Eric Rutaganda Placide Kamali François Ngabonziza Rei Ishikawa Belson Rugwizangoga Yuji Iwashita Hidetaka Yamada Kimio Yoshimura Haruhiko Sugimura Kazuya Shinmura |
| author_sort | Augustin Nzitakera |
| collection | DOAJ |
| description | Abstract Background Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. Results Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon–intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. Conclusions Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda. |
| first_indexed | 2024-04-24T12:36:47Z |
| format | Article |
| id | doaj.art-ec91c9212ec340219232c4764b265bf0 |
| institution | Directory Open Access Journal |
| issn | 1880-7062 |
| language | English |
| last_indexed | 2024-04-24T12:36:47Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Genes and Environment |
| spelling | doaj.art-ec91c9212ec340219232c4764b265bf02024-04-07T11:31:01ZengBMCGenes and Environment1880-70622024-03-0146111610.1186/s41021-024-00302-yThe spectrum of TP53 mutations in Rwandan patients with gastric cancerAugustin Nzitakera0Jean Bosco Surwumwe1Ella Larissa Ndoricyimpaye2Schifra Uwamungu3Delphine Uwamariya4Felix Manirakiza5Marie Claire Ndayisaba6Gervais Ntakirutimana7Benoit Seminega8Vincent Dusabejambo9Eric Rutaganda10Placide Kamali11François Ngabonziza12Rei Ishikawa13Belson Rugwizangoga14Yuji Iwashita15Hidetaka Yamada16Kimio Yoshimura17Haruhiko Sugimura18Kazuya Shinmura19Department of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Pathology, University Teaching Hospital of KigaliDepartment of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of RwandaDepartment of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of RwandaDepartment of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of RwandaDepartment of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Pathology, University Teaching Hospital of KigaliDepartment of Pathology, University Teaching Hospital of KigaliDepartment of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of RwandaDepartment of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of RwandaDepartment of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of RwandaDepartment of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of RwandaDepartment of Pathology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of RwandaDepartment of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Pathology, University Teaching Hospital of KigaliDepartment of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Health Policy and Management, Keio University School of MedicineDepartment of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Department of Tumor Pathology, Hamamatsu University School of Medicine (HUSM)Abstract Background Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. Results Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon–intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. Conclusions Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.https://doi.org/10.1186/s41021-024-00302-yTP53Mutation spectrumMutation patternGenetic analysisGastric cancerRwanda |
| spellingShingle | Augustin Nzitakera Jean Bosco Surwumwe Ella Larissa Ndoricyimpaye Schifra Uwamungu Delphine Uwamariya Felix Manirakiza Marie Claire Ndayisaba Gervais Ntakirutimana Benoit Seminega Vincent Dusabejambo Eric Rutaganda Placide Kamali François Ngabonziza Rei Ishikawa Belson Rugwizangoga Yuji Iwashita Hidetaka Yamada Kimio Yoshimura Haruhiko Sugimura Kazuya Shinmura The spectrum of TP53 mutations in Rwandan patients with gastric cancer Genes and Environment TP53 Mutation spectrum Mutation pattern Genetic analysis Gastric cancer Rwanda |
| title | The spectrum of TP53 mutations in Rwandan patients with gastric cancer |
| title_full | The spectrum of TP53 mutations in Rwandan patients with gastric cancer |
| title_fullStr | The spectrum of TP53 mutations in Rwandan patients with gastric cancer |
| title_full_unstemmed | The spectrum of TP53 mutations in Rwandan patients with gastric cancer |
| title_short | The spectrum of TP53 mutations in Rwandan patients with gastric cancer |
| title_sort | spectrum of tp53 mutations in rwandan patients with gastric cancer |
| topic | TP53 Mutation spectrum Mutation pattern Genetic analysis Gastric cancer Rwanda |
| url | https://doi.org/10.1186/s41021-024-00302-y |
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