Abstract：
Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4). This translocation is believed to involve the fusion of NSD3 or FGFR1 with NUP98; however, apart from targeted mRNA quantitative PCR analysis, no molecular approaches have been utilized to define the chimeric fusions present in these rare cases.
Here we present the case of a 51-year-old female with AML with myelodysplastic-related morphologic changes, 13q deletion and t(8;11), where initial fluorescence in situ hybridization (FISH) assays were consistent with the presence of NUP98 and FGFR1 rearrangements, and suggestive of NUP98/FGFR1 fusion. Using a streamlined clinical whole-genome sequencing approach, we resolved the breakpoints of this translocation to intron 4 of NSD3 and intron 12 of NUP98, indicating NUP98/NSD3 rearrangement as the likely underlying aberration. Furthermore, our approach identified small variants in WT1 and STAG2, as well as an interstitial deletion on the short arm of chromosome 12, which were cryptic in G-banded chromosomes.
NUP98 fusions in acute leukemia are predictive of poor prognosis. The associated fusion partner and the presence of co-occurring mutations, such as WT1, further refine this prognosis with potential clinical implications. Using a clinical whole-genome sequencing analysis, we resolved t(8;11) breakpoints to NSD3 and NUP98, ruling out the involvement of FGFR1 suggested by FISH while also identifying multiple chromosomal and sequence level aberrations.
Here we present the case of a 51-year-old female with AML with myelodysplastic-related morphologic changes, 13q deletion and t(8;11), where initial fluorescence in situ hybridization (FISH) assays were consistent with the presence of NUP98 and FGFR1 rearrangements, and suggestive of NUP98/FGFR1 fusion. Using a streamlined clinical whole-genome sequencing approach, we resolved the breakpoints of this translocation to intron 4 of NSD3 and intron 12 of NUP98, indicating NUP98/NSD3 rearrangement as the likely underlying aberration. Furthermore, our approach identified small variants in WT1 and STAG2, as well as an interstitial deletion on the short arm of chromosome 12, which were cryptic in G-banded chromosomes.
NUP98 fusions in acute leukemia are predictive of poor prognosis. The associated fusion partner and the presence of co-occurring mutations, such as WT1, further refine this prognosis with potential clinical implications. Using a clinical whole-genome sequencing analysis, we resolved t(8;11) breakpoints to NSD3 and NUP98, ruling out the involvement of FGFR1 suggested by FISH while also identifying multiple chromosomal and sequence level aberrations.
摘要：
背景：只有罕见的急性髓细胞性白血病（AML）病例显示存在t（8;11）（p11.2;p15.4）。这种易位被认为涉及NSD3或FGFR1与NUP98的融合;然而，除了靶向mRNA定量PCR分析，尚未使用分子方法来定义这些罕见病例中存在的嵌合融合。
方法：这里我们介绍一个51岁的AML患者的骨髓增生异常相关的形态学改变，13q删除和t(8;11)，其中初始荧光原位杂交（FISH）测定与NUP98和FGFR1重排的存在一致，并提示NUP98/FGFR1融合。使用简化的临床全基因组测序方法，我们解决了NSD3内含子4和NUP98内含子12易位的断点，表明NUP98/NSD3重排可能是潜在的畸变。此外，我们的方法确定了WT1和STAG2中的小变异,以及12号染色体短臂上的间质缺失,这在G带染色体中是隐匿的.
结论：NUP98融合在急性白血病中预测预后不良。相关的融合伴侣和共存突变的存在，如WT1，进一步改善这种预后，具有潜在的临床意义。使用临床全基因组测序分析，我们解决了NSD3和NUP98的t（8;11）断点，排除了FISH建议的FGFR1参与，同时还鉴定了多个染色体和序列水平的畸变。
方法：这里我们介绍一个51岁的AML患者的骨髓增生异常相关的形态学改变，13q删除和t(8;11)，其中初始荧光原位杂交（FISH）测定与NUP98和FGFR1重排的存在一致，并提示NUP98/FGFR1融合。使用简化的临床全基因组测序方法，我们解决了NSD3内含子4和NUP98内含子12易位的断点，表明NUP98/NSD3重排可能是潜在的畸变。此外，我们的方法确定了WT1和STAG2中的小变异,以及12号染色体短臂上的间质缺失,这在G带染色体中是隐匿的.
结论：NUP98融合在急性白血病中预测预后不良。相关的融合伴侣和共存突变的存在，如WT1，进一步改善这种预后，具有潜在的临床意义。使用临床全基因组测序分析，我们解决了NSD3和NUP98的t（8;11）断点，排除了FISH建议的FGFR1参与，同时还鉴定了多个染色体和序列水平的畸变。
