The spectrum of TP53 mutations in Rwandan patients with gastric cancer.

IF 2.7 4区 医学 Q2 GENETICS & HEREDITY
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
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引用次数: 0

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.

卢旺达胃癌患者的 TP53 基因突变谱。
背景:胃癌是全球第六大最常诊断出的癌症,也是全球第三大导致癌症相关死亡的癌症。人类癌症中最常见的突变基因是 TP53,它在癌症的发生和发展中起着关键作用。在非洲,尤其是卢旺达,缺乏有关 TP53 基因突变的数据。因此,本研究旨在了解卢旺达胃癌患者的 TP53 基因突变情况:从基加利大学教学医院获得了95名经组织病理学证实的卢旺达胃癌患者的福尔马林固定石蜡包埋组织块。提取 DNA 后,使用 Sanger 测序法对 TP53 基因的所有编码区和外显子-内含子边界区进行了测序。在 95 例病例中,有 24 例(25.3%)观察到 TP53 基因突变,共发现 29 个基因突变。这些TP53突变分布在第4和第8外显子之间,其中大部分为错义突变(19/29;65.5%)。TP53免疫组化分析显示,大多数TP53错义突变与TP53蛋白积累有关。在 29 个突变中,有一个是新突变(c.459_477delCGGCACCCGCGTCCGCGCC)。这个位于第 5 外显子的 19-bp 缺失突变导致产生截短的 TP53 蛋白(p.G154Wfs*10)。就 TP53 突变谱而言,CpG 位点上的 G:C > A:T 最常见(10/29;34.5%),G:C > T:A 次之(7/29;24.1%)。有趣的是,当将 TP53 的突变谱与之前针对非卢旺达籍胃癌患者的三项 TP53 突变研究进行比较时,本研究中 G:C > T:A 突变的发生率明显高于我们之前的研究(p = 0.013)、TCGA 数据库(p = 0.017)和之前针对香港患者的研究(p = 0.006)。即使校正了错误发现,仍观察到统计学意义:我们的研究结果表明,TP53 G:C > T:A 转换突变在卢旺达胃癌患者中的发生率高于非卢旺达胃癌患者,这表明卢旺达胃癌的病因和致癌进展可能是另一种情况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes and Environment
Genes and Environment Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
4.00
自引率
0.00%
发文量
24
审稿时长
27 weeks
期刊介绍: Genes and Environment is an open access, peer-reviewed journal that aims to accelerate communications among global scientists working in the field of genes and environment. The journal publishes articles across a broad range of topics including environmental mutagenesis and carcinogenesis, environmental genomics and epigenetics, molecular epidemiology, genetic toxicology and regulatory sciences. Topics published in the journal include, but are not limited to, mutagenesis and anti-mutagenesis in bacteria; genotoxicity in mammalian somatic cells; genotoxicity in germ cells; replication and repair; DNA damage; metabolic activation and inactivation; water and air pollution; ROS, NO and photoactivation; pharmaceuticals and anticancer agents; radiation; endocrine disrupters; indirect mutagenesis; threshold; new techniques for environmental mutagenesis studies; DNA methylation (enzymatic); structure activity relationship; chemoprevention of cancer; regulatory science. Genetic toxicology including risk evaluation for human health, validation studies on testing methods and subjects of guidelines for regulation of chemicals are also within its scope.
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