Evidence map›Paper›PMID 30548174›Full record

ArticleMolecular oncology2019

Molecular characterization of an MLL1 fusion and its role in chromosomal instability.

Sreejit Parameswaran, Frederick S Vizeacoumar, Kalpana Kalyanasundaram Bhanumathy, Fujun Qin, Md Fahmid Islam, Behzad M Toosi, Chelsea E Cunningham, Darrell D Mousseau, Maruti C Uppalapati, Peter C Stirling and 5 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.2field-weighted citation impact, top 51% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Targeting the undruggable: menin inhibitors ante portas.Journal of cancer research and clinical oncology · 2023
    Review
  3. Review
  4. The role of RNAMolecular therapy. Nucleic acids · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

Sreejit ParameswaranDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Frederick S VizeacoumarDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Kalpana Kalyanasundaram BhanumathyDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Fujun QinDepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Md Fahmid IslamDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Behzad M ToosiDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Chelsea E CunninghamDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Darrell D MousseauCell Signaling Laboratory, Departments of Psychiatry and Physiology, University of Saskatchewan, Saskatoon, Canada.
Maruti C UppalapatiDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Peter C StirlingTerry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Yuliang WuDepartment of Biochemistry, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Keith BonhamCancer Research, Saskatchewan Cancer Agency, Saskatoon, Canada.
Andrew FreywaldDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Hui LiDepartment of Pathology, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Franco J VizeacoumarDepartment of Pathology and Laboratory Medicine, Cancer Cluster, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Saskatchewan Cancer Agency · CAUniversity of Saskatchewan · CAUniversity of Virginia · USBC Cancer Agency · CA

Funding

Canadian Breast Cancer FoundationCanadian Foundation for Innovation CFI-33364Movember Prostate Discovery Grant D2015-14NSERC Discovery grantDiscovery Grant RGPIN-2014-04110Saskatchewan Cancer AgencySaskatchewan Health Research Foundation SHRF-3538
6 · The paper itself

Abstract

Chromosomal rearrangements involving the mixed-lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone. However, do these fusions occur or have a role in solid tumors? We performed extensive network analyses of MLL1-fusion partners in patient datasets, revealing that multiple MLL1-fusion partners exhibited significant interactions with the androgen-receptor signaling pathway. Further exploration of tumor sequence data from TCGA predicts the presence of MLL1 fusions with truncated SET domain in prostate tumors. To investigate the physiological relevance of MLL1 fusions in solid tumors, we engineered a truncated version of MLL1 by fusing it with one of its known fusion partners, ZC3H13, to use as a model system. Functional characterization with cell-based assays revealed that MLL1-ZC3H13 fusion induced chromosomal instability, affected mitotic progression, and enhanced tumorsphere formation. The MLL1-ZC3H13 chimera consistently increased the expression of a cancer stem cell marker (CD44); in addition, we detected potential collateral lethality between DOT1L and MLL1 fusions. Our work reveals that MLL1 fusions are likely prevalent in solid tumors and exhibit a potential pro-tumorigenic role.

Indexed as

Oncogene FusionBase SequenceBiomarkers, TumorCarcinogenesisCell Cycle ProteinsChromosomal InstabilityClone CellsGene Regulatory NetworksHCT116 CellsHumansModels, BiologicalMyeloid-Lymphoid Leukemia ProteinNuclear ProteinsOncogene Proteins, FusionPhenotypeRecombinant Fusion ProteinsBiomarkers, TumorCell Cycle ProteinsMyeloid-Lymphoid Leukemia ProteinNuclear ProteinsOncogene Proteins, FusionRecombinant Fusion ProteinsRNA-Binding ProteinsZC3H13 protein, humanchromosomal instabilitychromosomal rearrangementfusion proteinsmitotic checkpointtumor heterogeneity

Identifiers

PMID30548174
PMCPMC6360371
OpenAlexW2905035197

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.