Identification of a novel <i>RUNX1‐TACC1</i> fusion transcript in acute myeloid leukaemia

Yang, Ruyu; Yang, Chunxiao; Lang, Xingping; Duan, Li; Wang, Rui‐Juan; Zhou, Wei; Wu, Guangsheng; Li, Yonghui; Qian, Tingting; Xiao, Sheng; Fu, Lin

doi:10.1111/bjh.16444

Cited by 3 publications

(2 citation statements)

References 14 publications

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“…Interestingly, TACC1 association with the RUNX family occurred in cancer of the myeloid line. TACC domain induced the RUNX1-TACC1 fusion that resulted in myeloid leukemogenesis [ 26 ]. Knowing that RUNX3 shows similar DNA binding activity to RUNX1, it leaves the field to further investigation.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis

2023

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The runt-related transcription factor 3 (RUNX3) regulates the differentiation of monocytes and their response to inflammation. However, the transcriptomic context of RUNX3 expression in blood monocytes remains poorly understood. We aim to learn about RUNX3 from its relationships within transcriptomes of bulk CD14+ cells in adults. This study used immunomagnetically sorted CD14+ cell gene expression microarray data from the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1202, GSE56047) and the Correlated Expression and Disease Association Research (CEDAR, n = 281, E-MTAB-6667) cohorts. The data were preprocessed, subjected to RUNX3-focused correlation analyses and random forest modeling, followed by the gene ontology analysis. Immunity-focused differential ratio analysis with intermediary inference (DRAIMI) was used to integrate the data with protein–protein interaction network. Correlation analysis of RUNX3 expression revealed the strongest positive association for EVL (rmean = 0.75, pFDR-MESA = 5.37 × 10−140, pFDR-CEDAR = 5.52 × 10−80), ARHGAP17 (rmean = 0.74, pFDR-MESA = 1.13 × 10−169, pFDR-CEDAR = 9.20 × 10−59), DNMT1 (rmean = 0.74, pFDR-MESA = 1.10 × 10−169, pFDR-CEDAR = 1.67 × 10−58), and CLEC16A (rmean = 0.72, pFDR-MESA = 3.51 × 10−154, pFDR-CEDAR = 2.27 × 10−55), while the top negative correlates were C2ORF76 (rmean = −0.57, pFDR-MESA = 8.70 × 10−94, pFDR-CEDAR = 1.31 × 10−25) and TBC1D7 (rmean = −0.55, pFDR-MESA = 1.36 × 10−69, pFDR-CEDAR = 7.81 × 10−30). The RUNX3-associated transcriptome signature was involved in mRNA metabolism, signal transduction, and the organization of cytoskeleton, chromosomes, and chromatin, which may all accompany mitosis. Transcriptomic context of RUNX3 expression in monocytes hints at its relationship with cell growth, shape maintenance, and aspects of the immune response, including tyrosine kinases.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis

2023

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“…Moreover, the clinical features of patients depend on the functional defect of the fusion partner gene of ZNF384 (10). Fusion transcripts, chimeric RNAs encoded by fusion genes or generated through subsequent cissplicing and trans-splicing of mRNA in the absence of DNA rearrangements, serve as frequent drivers in a wide range of tumor types (11)(12)(13). Many fusion transcripts preferentially present in tumors compared to normal tissues, and contribute to tumor progression by enhancing cell proliferation and invasion (14).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer

et al. 2021

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BackgroundTriple-negative breast cancer (TNBC) is a highly aggressive cancer with poor prognosis. The lack of effective targeted therapies for TNBC remains a profound clinical challenge. Fusion transcripts play critical roles in carcinogenesis and serve as valuable diagnostic and therapeutic targets in cancer. The present study aimed to identify novel fusion transcripts in TNBC.MethodsWe analyzed the RNA sequencing data of 360 TNBC samples to identify and filter fusion candidates through SOAPfuse and ChimeraScan analysis. The characteristics, including recurrence, fusion type, chromosomal localization, TNBC subgroup distribution, and clinicopathological correlations, were analyzed in all candidates. Furthermore, we selected the promising fusion transcript and predicted its fusion type and protein coding capacity.ResultsUsing the RNA sequencing data, we identified 189 fusion transcripts in TNBC, among which 22 were recurrent fusions. Compared to para-tumor tissues, TNBC tumor tissues accumulated more fusion events, especially in high-grade tumors. Interestingly, these events were enriched at specific chromosomal loci, and the distribution pattern varied in different TNBC subtypes. The vast majority of fusion partners were discovered on chromosomes 1p, 11q, 19p, and 19q. Besides, fusion events mainly clustered on chromosome 11 in the immunomodulatory subtype and chromosome 19 in the luminal androgen receptor subtype of TNBC. Considering the tumor specificity and frameshift mutation, we selected MFGE8-HAPLN3 as a novel biomarker and further validated it in TNBC samples using PCR and Sanger sequencing. Further, we successfully identified three types of MFGE8-HAPLN3 (E6-E2, E5-E3, and E6-E3) and predicted the ORF of E6-E2, which could encode a protein of 712 amino acids, suggesting its critical role in TNBC.ConclusionsImproved bioinformatic stratification and comprehensive analysis identified the fusion transcript MFGE8-HAPLN3 as a novel biomarker with promising clinical application in the future.

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WNT inhibitory factor 1 (WIF1) is a novel fusion partner of RUNX family transcription factor 1 (RUNX1) in acute myeloid leukemia with t(12;21)(q14;q22)

Yang,

Sun,

Chen

et al. 2024

J Hematopathol

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Identification of a novel RUNX1‐TACC1 fusion transcript in acute myeloid leukaemia

Cited by 3 publications

References 14 publications

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis

Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer

WNT inhibitory factor 1 (WIF1) is a novel fusion partner of RUNX family transcription factor 1 (RUNX1) in acute myeloid leukemia with t(12;21)(q14;q22)

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