Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study
Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study
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DOI：
10.1182/blood-2009-07-234229
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发表时间：
2010-04-15
期刊：
影响因子：
20.3
通讯作者：
Broccardo, Cyril
中科院分区：
文献类型：
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作者：
Coyaud, Etienne;Struski, Stephanie;Broccardo, Cyril
PAX 5是急性B淋巴细胞白血病（B-ALL）体细胞突变的主要靶点。我们分析了153例成人和儿童B-ALL在染色体9 p处的核型异常，以确定PAX 5改变的频率和性质。我们在21%的病例中发现了PAX 5内部重排。为了分离融合伴侣，我们使用了经典和创新的技术（滚环扩增-cDNA末端的快速扩增）和单核苷酸多态性-比较基因组杂交阵列。鉴定了复发和新的融合伴侣，包括NCoR 1、DACH 2、GOLGA 6和TAOK 1基因，显示了伴侣的高变异性。我们注意到，一半的融合基因可以产生截短的PAX 5蛋白。此外，携带PAX 5融合基因的恶性细胞显示简单的核型。这些数据有力地表明PAX 5融合基因是白血病发生的早期参与者。此外，PAX 5缺失在60%的B-ALL中观察到9 p改变。与PAX 5融合的病例相反，缺失与复杂的核型和常见的复发性易位相关。这支持了删除的次要性质的假设。我们的数据揭示了B-ALL中PAX 5变异的高变异性。因此，基因融合很可能发生在早期，而缺失应被视为晚期/继发事件。（血。2010;115（15）：3089-3097）
PAX5 is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). We analyzed 153 adult and child B-ALL harboring karyotypic abnormalities at chromosome 9p, to determine the frequency and the nature of PAX5 alterations. We found PAX5 internal rearrangements in 21% of the cases. To isolate fusion partners, we used classic and innovative techniques (rolling circle amplification-rapid amplification of cDNA ends) and single nucleotide polymorphism-comparative genomic hybridization arrays. Recurrent and novel fusion partners were identified, including NCoR1, DACH2, GOLGA6, and TAOK1 genes showing the high variability of the partners. We noted that half the fusion genes can give rise to truncated PAX5 proteins. Furthermore, malignant cells carrying PAX5 fusion genes displayed a simple karyotype. These data strongly suggest that PAX5 fusion genes are early players in leukemogenesis. In addition, PAX5 deletion was observed in 60% of B-ALL with 9p alterations. Contrary to cases with PAX5 fusions, deletions were associated with complex karyotypes and common recurrent translocations. This supports the hypothesis of the secondary nature of the deletion. Our data shed more light on the high variability of PAX5 alterations in B-ALL. Therefore, it is probable that gene fusions occur early, whereas deletions should be regarded as a late/secondary event. (Blood. 2010;115(15):3089-3097)