PDF(Pubmed)
Abstract：
UNASSIGNED: Lower-risk myelodysplastic neoplasms (LR-MDS) comprise the majority of MDS. Despite favourable prognoses, some patients remain at risk of rapid progression. We aimed to define the mutational profile of LR-MDS using next-generation sequencing (NGS), Sanger Sequencing (SSeq), and pyrosequencing.
UNASSIGNED: Samples from 5 primary LR-MDS (67 exons of SF3B1, U2AF1, SRSF2, ZRSR2, TET2, ASXL1, DNMT3A, TP53, and RUNX1 genes) were subjected to NGS. Next, a genomic study was performed to test for the presence of identified DNA sequence variants on a larger group of LR-MDS patients (25 bone marrow [BM], 3 saliva [SAL], and one peripheral blood [PB] sample/s). Both SSeq (all selected DNA sequence variants) and pyrosequencing (9 selected DNA sequence variants) were performed.
UNASSIGNED: Next-generation sequencing results identified 13 DNA sequence variants in 7 genes, comprising 8 mutations in 6 genes (ASXL1, DNMT3A, RUNX1, SF3B1, TET2, ZRSR2) in LR-MDS. The presence of 8 DNA variants was detected in the expanded LR-MDS group using SSeq and pyrosequencing. Mutation acquisition was observed during LR-MDS progression. Four LR-MDS and one acute myeloid leukaemia myelodysplasia-related patient exhibited the presence of at least one mutation. ASXL1 and SF3B1 alterations were most commonly observed (2 patients). Five DNA sequence variants detected in BM (patients: 9, 13) were also present in SAL.
UNASSIGNED: We suggest using NGS to determine the LR-MDS mutational profile at diagnosis and suspicion of disease progression. Moreover, PB and SAL molecular testing represent useful tools for monitoring LR-MDS at higher risk of progression. However, the results need to be confirmed in a larger group.
UNASSIGNED: Samples from 5 primary LR-MDS (67 exons of SF3B1, U2AF1, SRSF2, ZRSR2, TET2, ASXL1, DNMT3A, TP53, and RUNX1 genes) were subjected to NGS. Next, a genomic study was performed to test for the presence of identified DNA sequence variants on a larger group of LR-MDS patients (25 bone marrow [BM], 3 saliva [SAL], and one peripheral blood [PB] sample/s). Both SSeq (all selected DNA sequence variants) and pyrosequencing (9 selected DNA sequence variants) were performed.
UNASSIGNED: Next-generation sequencing results identified 13 DNA sequence variants in 7 genes, comprising 8 mutations in 6 genes (ASXL1, DNMT3A, RUNX1, SF3B1, TET2, ZRSR2) in LR-MDS. The presence of 8 DNA variants was detected in the expanded LR-MDS group using SSeq and pyrosequencing. Mutation acquisition was observed during LR-MDS progression. Four LR-MDS and one acute myeloid leukaemia myelodysplasia-related patient exhibited the presence of at least one mutation. ASXL1 and SF3B1 alterations were most commonly observed (2 patients). Five DNA sequence variants detected in BM (patients: 9, 13) were also present in SAL.
UNASSIGNED: We suggest using NGS to determine the LR-MDS mutational profile at diagnosis and suspicion of disease progression. Moreover, PB and SAL molecular testing represent useful tools for monitoring LR-MDS at higher risk of progression. However, the results need to be confirmed in a larger group.
摘要：
■低危骨髓增生异常肿瘤（LR-MDS）占MDS的大部分。尽管预后良好，一些患者仍有快速进展的风险.我们旨在使用下一代测序（NGS）定义LR-MDS的突变谱，Sanger测序(SSeq),和焦磷酸测序。
■来自5个主要LR-MDS（SF3B1，U2AF1，SRSF2，ZRSR2，TET2，ASXL1，DNMT3A的67个外显子，TP53和RUNX1基因）进行NGS。接下来,进行了一项基因组研究，以测试在更大的一组LR-MDS患者中是否存在已识别的DNA序列变异（25骨髓[BM]，3唾液[SAL]，和一份外周血[PB]样本/s)。进行SSeq(所有选择的DNA序列变体)和焦磷酸测序(9个选择的DNA序列变体)。
■下一代测序结果确定了7个基因中的13个DNA序列变体，在6个基因中包含8个突变(ASXL1、DNMT3A、RUNX1，SF3B1，TET2，ZRSR2）在LR-MDS中。使用SSeq和焦磷酸测序在扩增的LR-MDS组中检测到8种DNA变体的存在。在LR-MDS进展期间观察到突变采集。四名LR-MDS和一名急性髓性白血病骨髓增生异常相关患者表现出至少一种突变。ASXL1和SF3B1改变最常见(2例)。在BM中检测到的五个DNA序列变体(患者:9,13)也存在于SAL中。
■我们建议在诊断和怀疑疾病进展时使用NGS来确定LR-MDS突变谱。此外，PB和SAL分子检测是监测进展风险较高的LR-MDS的有用工具。然而,结果需要在更大的群体中确认。
■来自5个主要LR-MDS（SF3B1，U2AF1，SRSF2，ZRSR2，TET2，ASXL1，DNMT3A的67个外显子，TP53和RUNX1基因）进行NGS。接下来,进行了一项基因组研究，以测试在更大的一组LR-MDS患者中是否存在已识别的DNA序列变异（25骨髓[BM]，3唾液[SAL]，和一份外周血[PB]样本/s)。进行SSeq(所有选择的DNA序列变体)和焦磷酸测序(9个选择的DNA序列变体)。
■下一代测序结果确定了7个基因中的13个DNA序列变体，在6个基因中包含8个突变(ASXL1、DNMT3A、RUNX1，SF3B1，TET2，ZRSR2）在LR-MDS中。使用SSeq和焦磷酸测序在扩增的LR-MDS组中检测到8种DNA变体的存在。在LR-MDS进展期间观察到突变采集。四名LR-MDS和一名急性髓性白血病骨髓增生异常相关患者表现出至少一种突变。ASXL1和SF3B1改变最常见(2例)。在BM中检测到的五个DNA序列变体(患者:9,13)也存在于SAL中。
■我们建议在诊断和怀疑疾病进展时使用NGS来确定LR-MDS突变谱。此外，PB和SAL分子检测是监测进展风险较高的LR-MDS的有用工具。然而,结果需要在更大的群体中确认。
