背景:本研究的目的是评估比较基因组杂交联合单核苷酸多态性微阵列(CGH/SNP)分析在小儿急性淋巴细胞白血病(ALL)风险分层中的一致性和附加值。
方法:这是一项回顾性研究,包括2016年至2021年在Sainte-Justine医院诊断为从头ALL的1-18岁患者。收集常规细胞遗传学和分子分析的结果,并与CGH/SNP的结果进行比较。
结果:共纳入135例ALL患者。样本失败或非诊断分析发生在17.8%的G带核型病例与1.5%的CGH/SNP病例中。CGH/SNP的结果平均周转时间明显快于核型,5.8天对10.7天,分别。通过CGH/SNP和G显带核型的倍性评估比较显示出很强的一致性(r=.82,p<.001,r2=.68)。此外,通过CGH/SNP和荧光原位杂交的组合分析,G显带核型未检测到其他临床相关畸变。CGH/SNP检测到的最常见的基因改变是涉及CDKN2A的缺失(35.8%),ETV6(31.3%),CDKN2B(28.4%),PAX5(20.1%),IKZF1(12.7%),拷贝中性杂合性丢失(CN-LOH)为9p(9.0%)。其中,在单变量和多变量分析中,仅ETV6缺失对预后有显著影响,且无事件生存率较好(校正风险比0.08,95%置信区间:0.01~0.50,p=.02).
结论:CGH/SNP提供的速度更快,可靠,与传统细胞遗传学获得的结果高度一致。CGH/SNP确定了小儿ALL中的复发性基因缺失,其中ETV6缺失赋予了良好的预后。
BACKGROUND: The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods.
METHODS: This is a retrospective study that included patients aged 1-18 years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP.
RESULTS: A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7 days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r = .82, p < .001, r2 = .68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p = .02).
CONCLUSIONS: CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional
cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.