Biological Sciences Division
Published February 9, 2022 | Version v1
Journal article Open

A functional genomic approach to actionable gene fusions for precision oncology

Creators

  • 1. University of Texas MD Anderson Cancer Center
  • 2. Baylor University
  • 3. Harvard University
  • 4. University of Chicago

Description

Fusion genes represent a class of attractive therapeutic targets. Thousands of fusion genes have been identified in patients with cancer, but the functional consequences and therapeutic implications of most of these remain largely unknown. Here, we develop a functional genomic approach that consists of efficient fusion reconstruction and sensitive cell viability and drug response assays. Applying this approach, we characterize ∼100 fusion genes detected in patient samples of The Cancer Genome Atlas, revealing a notable fraction of low-frequency fusions with activating effects on tumor growth. Focusing on those in the RTK-RAS pathway, we identify a number of activating fusions that can markedly affect sensitivity to relevant drugs. Last, we propose an integrated, level-of-evidence classification system to prioritize gene fusions systematically. Our study reiterates the urgent clinical need to incorporate similar functional genomic approaches to characterize gene fusions, thereby maximizing the utility of gene fusions for precision oncology.

Notes

Due to the large number of authors, only the first 20 and the University of Chicago authors are included on the above author list. Please download the article for the complete list of authors.

Data availability

All the data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Correspondence and requests for materials should be addressed to A.T. (athalham@sissa.it) and L.B. (laura.ballerini@sissa.it).

Files

sciadv.abm2382.pdf

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Additional details

Identifiers

DOI
10.1126/sciadv.abm2382
Other
oai:uchicago.tind.io:10907

Funding

National Institutes of Health
CA217842
National Institutes of Health
CA217685
National Institutes of Health
CA098258
National Institutes of Health
CA209851
National Institutes of Health
CA144025
National Institutes of Health
CA168394
National Institutes of Health
CA016672
National Institutes of Health
CA125123
Cancer Prevention and Research Institute of Texas
RP150535
Cancer Prevention and Research Institute of Texas
RP120046
Cancer Prevention and Research Institute of Texas
RP140102
Catching the Dream
National Institutes of Health
CA25347
Cancer Prevention and Research Institute of Texas
RR160021

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Ben May Department for Cancer Research, Human Genetics