Related Experiment Video

Updated: Dec 10, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.0K

Human transcription factor and protein kinase gene fusions in human cancer

Kari Salokas1, Rigbe G Weldatsadik1, Markku Varjosalo2

  • 1Systems Pathology/Biology Research Group, Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland.

Scientific Reports
|August 27, 2020
PubMed

Insights

Oncogenic gene fusions create functional proteins in nearly 30% of cases, impacting cancer. These fusions, particularly kinases and transcription factors, deregulate cellular signaling pathways, potentially driving cancer development.

Area of Science:

  • Genomics
  • Molecular Biology
  • Cancer Research

Background:

  • Oncogenic gene fusions contribute significantly to cancer morbidity, affecting various tissue types.
  • The functional consequences of many identified oncofusions remain largely unexplored.

Purpose of the Study:

  • To investigate the functional implications of oncogenic gene fusions identified through the DEEPEST approach.
  • To analyze the impact of oncofusions on protein function, domain architecture, and cellular signaling pathways.

Main Methods:

  • Analysis of 28,863 oncofusions identified by the DEEPEST fusion detection approach.
  • Examination of protein domain architecture and wild-type interactor data.
  • Differential gene expression analysis using The Cancer Genome Atlas (TCGA) samples.

Main Results:

  • Approximately 30% of identified oncofusions are predicted to yield functional chimeric proteins.
  • Kinase and transcription factor fusions were prevalent, suggesting their critical role in oncogenesis.
  • Oncofusions were associated with altered gene expression, particularly decreased levels of components in signal transduction and transcription regulation pathways.
  • Abnormal domain context in fusion proteins may activate oncogenic potential.

Conclusions:

  • Oncogenic gene fusions, especially those involving kinases and transcription factors, can acquire novel functions.
  • These fusions deregulate cellular signaling pathways, contributing to cancer development.
  • Further investigation into oncofusion mechanisms is crucial for understanding cancer etiology.

More Related Videos

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

9.9K
Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

7.3K

Related Concept Videos

Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
10.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.9K
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.5K
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
81.7K