Department of Human Genetics, Hannover Medical School, Hannover, Germany.
General Paediatrics, University Hospital Schleswig-Holstein, Kiel, Germany.
Genes Chromosomes Cancer. 2022 Jan;61(1):22-26. doi: 10.1002/gcc.22998. Epub 2021 Sep 13.
Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood and adolescence. In more than 60% of cases of this heterogeneous disease, a genetic marker is identified via cytogenetic or molecular analyses. TCF3 gene fusions occur in 5%-11% of ALL patients. In < 1%, the TCF3 alteration in ALL leads to a TCF3-HLF fusion gene. Even though this is a very rare event, the detection of a TCF3-HLF fusion gene is associated with a very poor prognosis with incurable relapses in almost all patients. The frequent TCF3-PBX1 fusion gene, which is detectable in 5%-10% of childhood B-cell precursor ALLs and ~3.8% of adult B-cell precursor ALLs, is associated with a rather good prognosis, that is, an observed event-free 5-year survival of approximately 85%. Thus, the distinction of the different partner genes fused to TCF3 is essential for risk assessment. To verify RNA sequencing as a tool for detection of known and unknown fusion genes, we screened 200 cases of pediatric B-cell precursor ALL with "targeted" RNA sequencing in a pilot project in comparison to classical cytogenetic analyses (chromosome R-banding analysis), fluorescence in situ hybridization, and PCR. We observed a TCF3 fusion gene in 6.5% (13/200) of the patients. Ten (5%) patients displayed a TCF3-PBX1 fusion gene, two (1%) patients a TCF3-FLI1 fusion gene, and one (0.5%) patient a TCF3-HLF fusion gene. For the TCF3 fusions, we obtained discrepant results with the different methods, which are described in the article. Taken together, translocations leading to TCF3 fusion genes might appear cryptic and may remain undetected by a single method.
急性淋巴细胞白血病（ALL）是儿童和青少年中最常见的恶性肿瘤。在这种异质性疾病的 60%以上的病例中，通过细胞遗传学或分子分析确定了一个遗传标志物。TCF3 基因融合发生在 ALL 患者的 5%-11%。在<1%的情况下，ALL 中的 TCF3 改变导致 TCF3-HLF 融合基因。尽管这是一种非常罕见的事件，但几乎所有患者都无法治愈的复发都与 ALL 中 TCF3-HLF 融合基因的检测相关，预后非常差。经常检测到的 TCF3-PBX1 融合基因，在 5%-10%的儿童 B 细胞前体 ALL 和~3.8%的成人 B 细胞前体 ALL 中可检测到，与相当好的预后相关，即观察到的无事件 5 年生存率约为 85%。因此，区分与 TCF3 融合的不同伴侣基因对于风险评估至关重要。为了验证 RNA 测序作为检测已知和未知融合基因的工具，我们在一个试点项目中对 200 例儿科 B 细胞前体 ALL 进行了“靶向”RNA 测序筛查，与经典细胞遗传学分析（染色体 R 带分析）、荧光原位杂交和 PCR 进行了比较。我们在 6.5%（13/200）的患者中观察到 TCF3 融合基因。10 名（5%）患者显示 TCF3-PBX1 融合基因，2 名（1%）患者显示 TCF3-FLI1 融合基因，1 名（0.5%）患者显示 TCF3-HLF 融合基因。对于 TCF3 融合基因，我们获得了与不同方法不一致的结果，文章中对此进行了描述。总之，导致 TCF3 融合基因的易位可能是隐匿的，并且可能无法通过单一方法检测到。
