PDF(Pubmed)
Abstract：
UNASSIGNED: Thanks to an improved therapeutic regimen in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 5 year-overall survival now exceeds 90%. Unfortunately, the 25% of children who relapse have an initial poor prognosis, potentially driven by pre-existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping.
UNASSIGNED: Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP-ALL and in a prospective cohort of 38 newly diagnosed childhood cases.
UNASSIGNED: In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B-cell development, cell proliferation, transcription and molecular pathways.
UNASSIGNED: SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.
UNASSIGNED: Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP-ALL and in a prospective cohort of 38 newly diagnosed childhood cases.
UNASSIGNED: In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B-cell development, cell proliferation, transcription and molecular pathways.
UNASSIGNED: SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.
摘要：
■由于改进了儿童B细胞前体急性淋巴细胞白血病（BCP-ALL）的治疗方案，5年总生存率现在超过90%。不幸的是,25%的复发儿童最初预后不良，可能由预先存在的或新出现的分子异常驱动。后者最初和基本上是通过细胞遗传学鉴定的。然而,一些细微的改变通过核型分析是不可见的。
单核苷酸多态性（SNP）阵列是染色体分析的另一种方法，可以更深入地评估染色体修饰，例如评估拷贝数改变（CNA）和杂合性缺失（LOH）。此方法适用于来自7名BCP-ALL儿童的回顾性诊断/复发配对样本以及38名新诊断儿童病例的前瞻性队列。
■在配对研究中，与最初的核型相比，SNP阵列分析将两名患者重新分类为预后不良病例。在复发期间观察到4个CNA和0.9个LOH的调节。在前瞻性研究中,SNP将10例中间核型患者重新分类为7例预后良好，3例预后不良。最终,在所有测试的孩子中，与常规核型相比，SNP阵列可以识别其他异常，完善其预后价值，并确定一些可用于精准医疗的药物异常。总的来说,检测到的异常可以分为四组，分别参与B细胞发育，细胞增殖，转录和分子途径。
■因此，SNP似乎是BCPALL综合诊断的一种选择方法，特别是对于最初分类为中间预后的患者。细胞遗传学和高通量测序两者的这种互补方法允许获得进一步的分类信息,并且在这些技术失败的情况下可以是有用的。
单核苷酸多态性（SNP）阵列是染色体分析的另一种方法，可以更深入地评估染色体修饰，例如评估拷贝数改变（CNA）和杂合性缺失（LOH）。此方法适用于来自7名BCP-ALL儿童的回顾性诊断/复发配对样本以及38名新诊断儿童病例的前瞻性队列。
■在配对研究中，与最初的核型相比，SNP阵列分析将两名患者重新分类为预后不良病例。在复发期间观察到4个CNA和0.9个LOH的调节。在前瞻性研究中,SNP将10例中间核型患者重新分类为7例预后良好，3例预后不良。最终,在所有测试的孩子中，与常规核型相比，SNP阵列可以识别其他异常，完善其预后价值，并确定一些可用于精准医疗的药物异常。总的来说,检测到的异常可以分为四组，分别参与B细胞发育，细胞增殖，转录和分子途径。
■因此，SNP似乎是BCPALL综合诊断的一种选择方法，特别是对于最初分类为中间预后的患者。细胞遗传学和高通量测序两者的这种互补方法允许获得进一步的分类信息,并且在这些技术失败的情况下可以是有用的。
