当前位置: X-MOL 学术Ann. Hematol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Implementation of RNA sequencing and array CGH in the diagnostic workflow of the AIEOP-BFM ALL 2017 trial on acute lymphoblastic leukemia.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-02-20 , DOI: 10.1007/s00277-020-03953-3
Maximilian Schieck 1 , Jana Lentes 1 , Kathrin Thomay 1 , Winfried Hofmann 1 , Yvonne Lisa Behrens 1 , Maike Hagedorn 1 , Juliane Ebersold 1 , Colin F Davenport 2 , Grazia Fazio 3 , Anja Möricke 4 , Swantje Buchmann 4 , Julia Alten 4 , Gunnar Cario 4 , Martin Schrappe 4 , Anke Katharina Bergmann 1 , Martin Stanulla 5 , Doris Steinemann 1 , Brigitte Schlegelberger 1 , Giovanni Cazzaniga 3 , Gudrun Göhring 1
Affiliation  

Risk-adapted therapy has significantly contributed to improved survival rates in pediatric acute lymphoblastic leukemia (ALL) and reliable detection of chromosomal aberrations is mandatory for risk group stratification. This study evaluated the applicability of panel-based RNA sequencing and array CGH within the diagnostic workflow of the German study group of the international AIEOP-BFM ALL 2017 trial. In a consecutive cohort of 117 children with B cell precursor (BCP) ALL, array analysis identified twelve cases with an IKZF1plus profile of gene deletions and one case of masked hypodiploidy. Genetic markers BCR-ABL1 (n = 1), ETV6-RUNX1 (n = 25), and rearrangements involving KMT2A (n = 3) or TCF3 (n = 3) were assessed by established conventional techniques such as karyotyping, FISH, and RT-PCR. Comparison of these results with RNA sequencing analysis revealed overall consistency in n=115/117 cases, albeit with one undetected AFF1-KMT2A fusion in RNA sequencing and one undetected ETV6-RUNX1 fusion in conventional analyses. The combined application of RNA sequencing, FISH, and CGH+SNP array reliably detected all genetic markers necessary for risk stratification and will be used as the diagnostic standard workflow for BCP-ALL patients enrolled in the AIEOP-BFM ALL 2017 study. Prospectively, consistent collection of genome-wide CGH+SNP array as well as RNA sequencing data will be a valuable source to elucidate new prognostic lesions beyond established markers of pediatric ALL. In this respect, RNA sequencing identified various gene fusions in up to half of the IKZF1plus (n = 6/12) and B-other (n = 19/36) cases but not in cases with hyperdiploid karyotypes (n = 35). Among these fusions, this study reports several previously undescribed in frame PAX5 fusions, including PAX5-MYO1G and PAX5-NCOA6.

中文翻译:

在AIEOP-BFM ALL 2017急性淋巴细胞白血病试验的诊断工作流程中实施RNA测序和阵列CGH。

适应风险的疗法显着提高了小儿急性淋巴细胞白血病(ALL)的生存率,对于危险人群分层,必须可靠地检测染色体畸变。这项研究在国际AIEOP-BFM ALL 2017试验的德国研究小组的诊断工作流程中评估了基于面板的RNA测序和阵列CGH的适用性。在连续的117例B细胞前体(BCP)ALL儿童中,阵列分析确定了12例基因缺失的IKZF1plus谱图和1例假二倍体。遗传标记BCR-ABL1(n = 1),ETV6-RUNX1(n = 25)和涉及KMT2A(n = 3)或TCF3(n = 3)的重排通过建立的常规技术进行了评估,例如核型分析,FISH和RT -PCR。将这些结果与RNA测序分析进行比较,发现在n = 115/117例病例中总体一致性,尽管在常规测序中有一个未检测到的AFF1-KMT2A融合和一个未检测到的ETV6-RUNX1融合。RNA测序,FISH和CGH + SNP阵列的组合应用可靠地检测了风险分层所需的所有遗传标记,并将用作参与AIEOP-BFM ALL 2017研究的BCP-ALL患者的诊断标准工作流程。潜在地,全基因组CGH + SNP阵列的一致收集以及RNA测序数据将是阐明超出儿科ALL既定标志物的新预后病变的宝贵来源。在这方面,RNA测序可在多达IKZF1plus(n = 6/12)和B-other(n = 19/36)的一半病例中鉴定出各种基因融合,但在超二倍体核型(n = 35)的病例中未鉴定出。在这些融合中,这项研究报告了几种以前在框架中未描述的PAX5融合,包括PAX5-MYO1G和PAX5-NCOA6。
更新日期:2020-02-20
down
wechat
bug