Abstract：
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.
摘要：
目标：以TP53变异为特征的MDS和AML总体预后不良。然而,具体来说,在TP53变体和VAF不同的患者中也观察到了预后的差异.方法:这里,我们回顾性分析了MDS患者的数据集，MPN,和AML患者在2018年2月至2023年12月期间接受了靶向DNA测序,并筛选了可报告TP53变异的患者.收集人口统计数据和临床数据，使用cBioPortal和Kaplan-MeierPlotter数据库分析TP53改变与患者预后(AML/MDS)之间的关系.使用本研究的数据分析了TP53变异的VAF与预后之间的关系。结果：在58例患者中发现了62种TP53变体。我们主要鉴定了单个突变（79.31%，46/58)，其次是两倍(17.24%，10/58）和三倍（3.45%，2/58）突变。变异主要富集在TP53的exon4-exon8中。Missense(72.58%，45/62)突变是变异的主要类型，其次是剪接位点(9.68%，6/62),胡说八道(9.68%，6/62),移码(6.45%，4/62),和indel(1.61%，1/62）突变。在这项研究中,p.Arg175His和p.Arg273His是高频率TP53突变，DNMT3A和TET2是三种髓系肿瘤中常见的共突变基因；然而，我们报道了一些在MPN中尚未在公共数据库中发现的新TP53变体.此外，以TP53改变为特征的MDS或AML的OS比未改变组的患者短(P<0.01),低TP53mRNA水平与AML患者OS较短相关(P<0.01)。我们中心的数据进一步发现，在MDS患者中，较高的VAF(≥10%)与较短的OS相关(中位数为2.75vs.24个月)(P<0.01)。结论:TP53突变主要富集在exon4-exon8,是髓系肿瘤的错义突变和单突变,并与MDS/AML的不良预后相关，在MDS患者中，TP53突变的较高VAF（≥10％）与较短的OS相关。
