Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu
{"title":"骨髓肿瘤患者中 TP53 的变异特征和临床意义。","authors":"Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu","doi":"10.1080/16078454.2024.2387878","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objectives:</b> MDS and AML characterized by <i>TP53</i> variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different <i>TP53</i> variants and VAFs.<b>Methods:</b> Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable <i>TP53</i> variations were screened. Demographic data and clinical data were collected, and the relationship between <i>TP53</i> alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of <i>TP53</i> variations and prognoses was analyzed using data from the present study.<b>Results:</b> Sixty-two variants of <i>TP53</i> were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of <i>TP53</i>. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency <i>TP53</i> mutations, and <i>DNMT3A</i> and <i>TET2</i> were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new <i>TP53</i> variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered <i>TP53</i> had a shorter OS than patients in the unaltered group (<i>P</i><0.01), low <i>TP53</i> mRNA levels were associated with shorter OS in patients with AML (<i>P</i><0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (<i>P</i><0.01).<b>Conclusion:</b> <i>TP53</i> mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of <i>TP53</i> mutations associated with a shorter OS in patients with MDS.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2387878"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Variation characteristics and clinical significance of <i>TP53</i> in patients with myeloid neoplasms.\",\"authors\":\"Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu\",\"doi\":\"10.1080/16078454.2024.2387878\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Objectives:</b> MDS and AML characterized by <i>TP53</i> variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different <i>TP53</i> variants and VAFs.<b>Methods:</b> Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable <i>TP53</i> variations were screened. Demographic data and clinical data were collected, and the relationship between <i>TP53</i> alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of <i>TP53</i> variations and prognoses was analyzed using data from the present study.<b>Results:</b> Sixty-two variants of <i>TP53</i> were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of <i>TP53</i>. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency <i>TP53</i> mutations, and <i>DNMT3A</i> and <i>TET2</i> were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new <i>TP53</i> variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered <i>TP53</i> had a shorter OS than patients in the unaltered group (<i>P</i><0.01), low <i>TP53</i> mRNA levels were associated with shorter OS in patients with AML (<i>P</i><0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (<i>P</i><0.01).<b>Conclusion:</b> <i>TP53</i> mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of <i>TP53</i> mutations associated with a shorter OS in patients with MDS.</p>\",\"PeriodicalId\":13161,\"journal\":{\"name\":\"Hematology\",\"volume\":\"29 1\",\"pages\":\"2387878\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/16078454.2024.2387878\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/16078454.2024.2387878","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Variation characteristics and clinical significance of TP53 in patients with myeloid neoplasms.
Objectives: MDS and AML characterized by TP53 variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different TP53 variants and VAFs.Methods: Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable TP53 variations were screened. Demographic data and clinical data were collected, and the relationship between TP53 alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of TP53 variations and prognoses was analyzed using data from the present study.Results: Sixty-two variants of TP53 were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of TP53. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency TP53 mutations, and DNMT3A and TET2 were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new TP53 variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered TP53 had a shorter OS than patients in the unaltered group (P<0.01), low TP53 mRNA levels were associated with shorter OS in patients with AML (P<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (P<0.01).Conclusion:TP53 mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of TP53 mutations associated with a shorter OS in patients with MDS.
期刊介绍:
Hematology is an international journal publishing original and review articles in the field of general hematology, including oncology, pathology, biology, clinical research and epidemiology. Of the fixed sections, annotations are accepted on any general or scientific field: technical annotations covering current laboratory practice in general hematology, blood transfusion and clinical trials, and current clinical practice reviews the consensus driven areas of care and management.