Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AMLI) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia
Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AMLI) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia
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DOI：
10.1002/gcc.1182
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发表时间：
2001-10-01
影响因子：
3.7
通讯作者：
Raimondi, SC
中科院分区：
文献类型：
--
作者：
Mathew, S;Shurtleff, SA;Raimondi, SC
在儿童B系急性淋巴细胞性白血病(ALL)中，最常见的基因变化是ETV6-CBFA2(TEL-AML1)融合：源于隐匿的t(12；21)(p13；q22)与良好的预后相关。因此，识别这种易位的患者是很重要的，这样他们才能接受适当的治疗来确定ETV6和CBFA2的新的伴侣断裂点。我们选择了30例儿童ALL患者，他们的白血病细胞a t(12；21)经RT-PCR检测到。常规细胞遗传学检查显示，10例患者存在12P异常，另有15例患者存在其他随机异常，其中9例伴有21号染色体的数量或结构异常。5例患者白血病细胞核型正常。间期荧光原位杂交(FISH)证实每例患者均存在t(12；21)，14例(47%)患者存在野生型ETV6等位基因缺失。只有20名患者的中期细胞可用于额外的FISH分析。在13例患者中，在der(21)t(12；21)上观察到预期的t(12；21)融合信号，在der(12)t(12；21)上观察到倒置的CBFA2信号。然而，在6例21号染色体ETV6-CSFA2融合的患者中，在4q21、4q27、8q24、11q24、14q11.2或16p13.1上观察到CBFA2信号的相互作用，而不是在12p13上。在这六名患者中的四名，我们发现CBFA2的部分间质插入。另一例ETV6-CBFA2融合发生在4q21，而不是21q。因此，在20名t(12；21)患者中，有7人(35%)表现出复杂的重排。我们的发现也表明了分析中期染色体在识别涉及ETV6和CBFA2的隐蔽和复杂重排方面的重要性。(C)2001年Wiley-Liss，Inc.
In, childhood B-lineage acute lymphoblastic leukemia (ALL), the most common genetic change, the ETV6-CBFA2 (TEL-AML1) fusion: resulting from the cryptic t(12;21)(p13;q22) is associated with a favorable outcome. Therefore, it is important to identify patients with this translocation so that they can receive appropriate treatment To identify new partner breakpoints for ETV6 and CBFA2, we selected 30 patients with childhood ALL in whose leukemic cells a t(12;21) had been detected by RT-PCR. Conventional cytogenetics revealed that 12p abnormalities were present in 10 patients and that other random abnormalities were present in another 15, including 9 with a numerical or structural abnormality of chromosome 21. Normal karyotypes were observed in the leukemic blasts of five patients. Interphase fluorescence in situ hybridization (FISH) confirmed the RT-PCR finding of the t(12;21) in each patient and detected the loss of the wild-type ETV6 allele in 14 (47%) patients. Metaphase cells from only 20 patients were available for additional FISH analysis. In 13 patients, the expected fusion signal of t(12;21) was observed on der(21)t(12;21), and the reciprocal CBFA2 signal was observed on der(12)t(12;21). However, in six patients with the ETV6-CSFA2 fusion on chromosome 21, the reciprocal CBFA2 signal was observed not on 12p 13 but on 4q21, 4q27, 8q24, 11q24, 14q11.2, or 16p13.1. In four of these six patients, we found interstitial insertions of part of CBFA2. In another patients the ETV6-CBFA2 fusion was observed on 4q21 rather than on 21q. Thus, seven (35%) of the 20 patients with a t(12;21) revealed complex rearrangements. Our findings also indicate the importance of analyzing metaphase chromosomes in identifying cryptic and complex rearrangements involving ETV6 and CBFA2. (C) 2001 Wiley-Liss, Inc.