Whole transcriptome sequencing detects a large number of novel fusion transcripts in patients with AML and MDS

被引:32
|
作者
Stengel, Anna [1 ]
Shahswar, Rabia [2 ]
Haferlach, Torsten [1 ]
Walter, Wencke [1 ]
Hutter, Stephan [1 ]
Meggendorfer, Manja [1 ]
Kern, Wolfgang [1 ]
Haferlach, Claudia [1 ]
机构
[1] MLL Munich Leukemia Lab, Max Lebsche Pl 31, D-81377 Munich, Germany
[2] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany
关键词
ACUTE MYELOID-LEUKEMIA; GENE; CLASSIFICATION; PROGNOSIS; DIAGNOSIS; DISEASE;
D O I
10.1182/bloodadvances.2020003007
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fusion transcripts are frequent genetic abnormalities in myeloid malignancies and are often the basis for risk stratification, minimal residual disease (MRD) monitoring, and targeted therapy. We comprehensively analyzed the fusion transcript landscape in 572 acute myeloid leukemia (AML) and 630 myelodysplastic syndrome (MDS) patients by whole transcriptome sequencing (WTS). Totally, 274 fusion events (131 unique fusions) were identified in 210/572 AML patients (37%). In 16/630 MDS patients, 16 fusion events (15 unique fusions) were detected (3%). In AML, 141 cases comprised entity-defining rearrangements (51% of all detected fusions) and 21 (8%) additional well-known fusions, all detected by WTS (control group). In MDS, only 1 fusion was described previously (NRIP1-MECOM, n = 2). Interestingly, a high number of so-far unreported fusions were found (41% [112/274] in AML, 88% [14/16] in MDS), all validated by cytogenetic and/or whole genome sequencing data. With 1 exception (CTDSP1-CFLAR, n = 2), all novel fusions were observed in 1 patient each. In AML, cases with novel fusions showed concomitantly a high frequency of TP53 mutations (67%) and of a complex karyotype (71%), which was also observed in MDS, but less pronounced (TP53, 26%; complex karyotype, 21%). A functional annotation of genes involved in novel fusions revealed many functional relevant genes (eg, transcription factors; n = 28 in AML, n = 2 in MDS) or enzymes (n = 42 in AML, n = 9 in MDS). Taken together, new genomic alterations leading to fusion transcripts were much more common in AML than in MDS. Any novel fusions might be of use for developing markers (eg, for MRD monitoring), particularly in cases without an entity-defining abnormality.
引用
收藏
页码:5393 / 5401
页数:9
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