Background TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

中文翻译：

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骨髓增生异常肿瘤和急性髓性白血病中的 TP53 突变状态：基于第 5 个 WHO 和国际共识分类标准重新分类的影响：一项韩国多中心研究。


背景 TP53 突变与骨髓增生异常肿瘤 （MDS） 和 AML 的不良预后相关。更新后的第 5 个 WHO 分类和国际共识分类 （ICC） 将 TP53 突变的 MDS 和 AML 归类为独特实体。我们在韩国进行了一项多中心研究，以调查 TP53 突变的 MDS 和 AML 的特征，重点关注基于更新分类的诊断方面。方法 本研究纳入了 6 个机构诊断为 MDS （N=1,244） 或 AML （N=2,115） 的 ≥ 18 岁患者。收集并分析骨髓检查、细胞遗传学研究和靶向下一代测序（包括 TP53）的结果。结果 在 MDS 和 AML 患者中分别检测到 TP53 突变和 9.2%。错义突变最常见，热点密码子 R248/R273/G245/Y220/R175/C238 占 TP53 突变的 25.4%。10% 的患者具有多个 TP53 突变，78.4% 的患者具有复杂的核型。TP53 突变的中位变异等位基因频率 （VAF） 为 41.5%，根据复杂核型的存在存在，存在显着差异。根据第 5 个 WHO 分类和 ICC，分别有 58.6% 和 75% 的 MDS 患者满足多次打击 TP53 突变标准，主要决定因素是第 5 个 WHO 分类的 TP53 VAF >50% 和 ICC 存在复杂核型。结论 总的来说，我们阐明了 TP53 突变 MDS 和 AML 患者的分子遗传学特征，强调了在更新的分类中应用 TP53 突变相关标准的关键因素，这将有助于建立诊断策略。