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Updated: Sep 4, 2025
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Pan-Cancer Analysis Reveals Recurrent BCAR4 Gene Fusions across Solid Tumors
Andrew Nickless1, Jin Zhang2,3,4, Ghofran Othoum1
1Division of Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Abstract:
Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation.
Implications:
BCAR4 gene fusions represent an underappreciated class of gene fusions that may have biological and clinical implications across solid tumors.
Insights
Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) gene fusions were found in 11 cancers. This long noncoding RNA drives proliferation and may play a significant role in solid tumor development.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Chromosomal rearrangements can create oncogenic gene fusions by juxtaposing regulatory elements with oncogenes.
- Common downstream partners in gene fusions suggest conserved oncogenic roles across different tumor types.
Purpose of the Study:
- To identify and characterize novel downstream gene fusion partners in solid tumors.
- To investigate the oncogenic role of the long noncoding RNA BCAR4 in cancer.
Main Methods:
- Analysis of 9,638 patients across 32 solid tumor types to identify gene fusions.
- Confirmation of oncogenic role using cell line models with endogenous BCAR4 gene fusions.
- Functional studies involving overexpression of BCAR4 gene fusions in untransformed cell lines.
Main Results:
- BCAR4 was identified as the most prevalent uncharacterized downstream gene fusion partner in 11 of 32 solid tumor types.
- Endogenous BCAR4 gene fusions confirmed its oncogenic role in multiple cell lines.
- Overexpression of BCAR4 gene fusions induced an oncogenic phenotype in untransformed cells.
- A minimal open reading frame within BCAR4 gene fusions was necessary for driving proliferation.
Conclusions:
- BCAR4 gene fusions represent a novel and underappreciated class of oncogenic drivers in solid tumors.
- BCAR4's role in proliferation highlights its potential as a therapeutic target across various cancer types.
- These findings have significant biological and clinical implications for understanding and treating solid tumors.
