Kritika Krishnamurthy, Kei Shing Oh, Sarah Alghamdi, Vathany Sriganeshan, Robert Poppiti
{"title":"体细胞BRCA变异及其对恶性间皮瘤蛋白特性的影响的研究。","authors":"Kritika Krishnamurthy, Kei Shing Oh, Sarah Alghamdi, Vathany Sriganeshan, Robert Poppiti","doi":"10.1515/pp-2023-0003","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study is to analyze the prevalence of somatic mutations in <i>BRCA1</i> and <i>BRCA2</i> in malignant mesothelioma and their putative impact on protein properties.</p><p><strong>Methods: </strong>Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of <i>BRCA1</i> and <i>BRCA2</i> genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server.</p><p><strong>Results: </strong><i>BRCA2</i> variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02).</p><p><strong>Conclusions: </strong><i>BRCA2</i> somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.</p>","PeriodicalId":20231,"journal":{"name":"Pleura and Peritoneum","volume":"8 1","pages":"19-25"},"PeriodicalIF":1.4000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067552/pdf/","citationCount":"0","resultStr":"{\"title\":\"A study of somatic <i>BRCA</i> variants and their putative effect on protein properties in malignant mesothelioma.\",\"authors\":\"Kritika Krishnamurthy, Kei Shing Oh, Sarah Alghamdi, Vathany Sriganeshan, Robert Poppiti\",\"doi\":\"10.1515/pp-2023-0003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The aim of this study is to analyze the prevalence of somatic mutations in <i>BRCA1</i> and <i>BRCA2</i> in malignant mesothelioma and their putative impact on protein properties.</p><p><strong>Methods: </strong>Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of <i>BRCA1</i> and <i>BRCA2</i> genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server.</p><p><strong>Results: </strong><i>BRCA2</i> variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02).</p><p><strong>Conclusions: </strong><i>BRCA2</i> somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.</p>\",\"PeriodicalId\":20231,\"journal\":{\"name\":\"Pleura and Peritoneum\",\"volume\":\"8 1\",\"pages\":\"19-25\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067552/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pleura and Peritoneum\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1515/pp-2023-0003\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pleura and Peritoneum","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/pp-2023-0003","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
A study of somatic BRCA variants and their putative effect on protein properties in malignant mesothelioma.
Objectives: The aim of this study is to analyze the prevalence of somatic mutations in BRCA1 and BRCA2 in malignant mesothelioma and their putative impact on protein properties.
Methods: Eighteen cases of malignant mesothelioma were retrieved from the archives and for next generation sequencing analysis of BRCA1 and BRCA2 genes. Variants were analyzed using Ensembl VEP17, Polyphen 2.0 software, SIFT software, MutpredV2, and SWISS-MODEL homology-modeling pipeline server.
Results: BRCA2 variants were found in significantly higher percentage (22%) of cases (p=0.02). Five missense variants were identified. These were p.A2351P, p.T2250A, p.A895V, pG1771D, and p.R2034C. The SIFT scores of all except one were ≥ 0.03. The Polyphen scores of these four alterations were ≤0.899. In case of p.A2315, the SIFT score was 0.01, while the Polyphen 2 score was 0.921. MutPred2 scores were ≤0.180 for all. Loss of intrinsic disorder was predicted (Pr=0.32, p=0.07) for p.R2034C, while gain of intrinsic disorder was predicted for p.A2351P (Pr=0.36, p=0.01) and p.G1771D (Pr=0.34, p=0.02).
Conclusions: BRCA2 somatic variants were identified in 22% cases of malignant mesotheliomas in this study. The variants localize more frequently to the disordered regions of the protein and are predicted to affect the level of disorder.
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