Ring chromosomes (RC) are present in <10% of patients with hematological malignancies and are associated with poor prognosis. Until now, only small cohorts of patients with hematological neoplasms and concomitant RCs have been cytogenetically characterized. Here, we performed a conventional chromosome analysis on metaphase spreads from >13,000 patients diagnosed with hematological malignancies at the Johns Hopkins University Hospital and identified 98 patients with RCs—90 with myeloid malignancies and 8 with lymphoid malignancies. We also performed a targeted Next-Generation Sequencing (NGS) assay, using a panel of 642 cancer genes, to identify whether these patients harbor relevant pathogenic variants. Cytogenetic analyses revealed that RCs and marker chromosomes of unknown origin are concurrently present in most patients by karyotyping, and 93% of patients with NGS data have complex karyotypes. A total of 72% of these individuals have pathogenic mutations inTP53, most of whom also possess cytogenetic abnormalities resulting in the loss of 17p, including the loss ofTP53. All patients with a detected RC and without complex karyotypes also lackTP53mutations but have pathogenic mutations inTET2.Further, 70% of RCs that map to a known chromosome are detected in individuals withoutTP53mutations. Our data suggest that RCs in hematological malignancies may arise through different mechanisms, but ultimately promote widespread chromosomal instability.
环形染色体在血液系统恶性肿瘤患者中的发生率低于10%，且与不良预后相关。迄今为止，仅对少数伴有环形染色体的血液肿瘤患者进行了细胞遗传学特征分析。本研究对约翰霍普金斯大学医院确诊的13,000余名血液恶性肿瘤患者进行中期染色体常规分析，共发现98例环形染色体携带者——其中90例为髓系恶性肿瘤，8例为淋巴系统恶性肿瘤。同时采用包含642个癌症基因的靶向二代测序技术，检测这些患者是否携带相关致病性变异。细胞遗传学分析显示，核型分析发现大多数患者同时存在环形染色体与来源不明的标记染色体，且93%获得二代测序数据的患者具有复杂核型。其中72%的患者存在TP53致病突变，且多数伴有导致17p缺失（包含TP53基因缺失）的细胞遗传学异常。所有检出环形染色体但无复杂核型的患者均未发现TP53突变，但存在TET2致病突变。此外，70%可定位至特定染色体的环形染色体出现于无TP53突变的个体中。我们的研究数据表明，血液系统恶性肿瘤中的环形染色体可能通过不同机制形成，但最终都会促进广泛的染色体不稳定性。
肿瘤(癌症)患者之家