Firtina Sinem, Erbilgin Yucel, Hatirnaz Ng Ozden, Karaman Serap, Karakas Zeynep, Celkan Tulin Tiraje, Gelen Sema Aylan, Yildirmak Yildiz, Ozbek Ugur, Sayitoglu Muge
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
Department of Medical Genetics, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey.
Scand J Clin Lab Invest. 2023 May;83(3):187-193. doi: 10.1080/00365513.2023.2195682. Epub 2023 Apr 8.
The () gene is one of the most studied genes in cancer. Although variants are rare events in acute leukemia, recent observations showed that relapse samples might harbor variants. Here, we aimed to determine variants (hotspot region, exon 4-11) in childhood acute lymphoblastic leukemia (B and T-ALL) patients ( = 94) including diagnostic-relapse pairs ( = 15) by amplicon sequencing and evaluate the clinical impact of these variants. In total, nine different (E298*, R283C, R273H, L252F, C229F, I195T, E286G, c.955_956insC, and c.920-1G > C) variants were identified in 17 (18%) childhood ALL patients. c.(920-1G> C) splice site variant and c.(955_956insC) insertion were reported for the first time. In diagnose-relapse pair samples, we identified acquired and/or loss of TP53 variants in the samples at the time of relapse. variants were found to be more common in T-ALL (37%) than in B-ALL patients (9%). Pathogenic variants were associated with a shorter overall survival time ( 0.001). variants were found to be associated with inferior outcomes in our cohort and can be an independent risk factor for poor prognosis in childhood acute leukemia patients. Identification of low-frequent variants with next-generation sequencing approaches enables better knowledge of the clonal dynamics of ALL.
（）基因是癌症研究中最深入的基因之一。虽然在急性白血病中变异是罕见事件，但最近的观察表明复发样本可能携带变异。在此，我们旨在通过扩增子测序确定儿童急性淋巴细胞白血病（B和T-ALL）患者（n = 94）包括诊断-复发配对样本（n = 15）中的变异（热点区域，外显子4-11），并评估这些变异的临床影响。总共在17例（18%）儿童ALL患者中鉴定出9种不同的（E298*、R283C、R273H、L252F、C229F、I195T、E286G、c.955_956insC和c.920-1G＞C）变异。c.（920-1G＞C）剪接位点变异和c.（955_956insC）插入首次被报道。在诊断-复发配对样本中，我们在复发时的样本中鉴定出TP53变异的获得和/或缺失。变异在T-ALL（37%）中比在B-ALL患者（9%）中更常见。致病性变异与较短的总生存时间相关（P＜0.001）。在我们的队列中发现变异与较差的预后相关，并且可能是儿童急性白血病患者预后不良的独立危险因素。用下一代测序方法鉴定低频变异能够更好地了解ALL的克隆动态。
