Claerhout Helena, Vranckx Hilde, Lierman Els, Michaux Lucienne, Boeckx Nancy
Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Center for Human Genetics, University Hospitals Leuven and KU Leuven, Leuven, Belgium.
Acta Clin Belg. 2022 Jun;77(3):658-663. doi: 10.1080/17843286.2021.1943232. Epub 2021 Jul 1.
Therapy-related myeloid neoplasms (t-MN) are frequently categorized according to previous therapy or pattern of cytogenetic abnormalities. Our objective was to evaluate and compare the mutational profile of and t-MN by next generation sequencing.
Sixty-four samples from patients with t-MN, previously treated for a solid tumor (mainly breast), or AML, MDS, MDS/MPN were selected for our study. The library was prepared using diagnostic samples and the TruSight Myeloid sequencing panel targeting 54 genes. Samples were sequenced on a MiSeq. The classification system of the Belgian ComPerMed Expert Panel was used for the biological variant classification.
Taking only pathogenic, probably pathogenic variants and variants of unknown significance into account 141 variants in 33 genes were found in 52 of 64 samples (81%; mean number of variants per patient = 2; range = [1-11]; 67 variants in 25 genes in t-MN and 74 variants in 25 genes in MN). Overall, the most frequently detected variants included (n = 22), (n = 12), (n = 10) and (n = 8 each).
Our study revealed a high variety of variants both in t-MN and MN patients. There was a higher incidence of and variants in t-MN compared to MN.
治疗相关髓系肿瘤（t-MN）通常根据既往治疗或细胞遗传学异常模式进行分类。我们的目的是通过下一代测序评估和比较t-MN和髓系肿瘤（MN）的突变谱。
我们选择了64例t-MN患者的样本进行研究，这些患者既往曾接受实体瘤（主要是乳腺癌）治疗，或患有急性髓系白血病（AML）、骨髓增生异常综合征（MDS）、骨髓增生异常/骨髓增殖性肿瘤（MDS/MPN）。使用诊断样本和靶向54个基因的TruSight Myeloid测序panel制备文库。样本在MiSeq上进行测序。采用比利时ComPerMed专家小组的分类系统进行生物学变异分类。
仅考虑致病性、可能致病性变异和意义未明的变异，在64个样本中的52个（81%）中发现了33个基因中的141个变异（每位患者变异的平均数 = 2；范围 = [1-11]；t-MN中25个基因有67个变异，MN中25个基因有74个变异）。总体而言，最常检测到的变异包括TP53（n = 22）、NRAS（n = 12）、FLT3（n = 10）和DNMT3A（各n = 8）。
我们的研究揭示了t-MN和MN患者中存在多种变异。与MN相比，t-MN中TP53和NRAS变异的发生率更高。
