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NRG1 Gene Fusions Detected at Low Incidence Across Multiple Tumor Types

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Key Points

  • Out of nearly 22,000 tumor specimens studied, 41 (0.2%) harbored an NRG1 fusion.
  • The greatest incidence of NRG1 fusion was in non–small lung cancer (though this represented only 0.3% of all non­–small cell lung cancers), but the gene fusion, best found through RNA sequencing, was also found in kidney, gallbladder, bladder, ovarian, pancreatic, breast, and colorectal cancers, as well as in sarcoma and neuroendocrine cancers.

A consortium of researchers have completed an analysis of a new gene fusion they believe is responsible for the development of a wide spectrum of cancer types. According to the investigators, their studies show that errant gene fusions in neuregulin-1, or NRG1, which are present in about 0.2% of cancers, may be targeted with existing agents or novel treatments. These findings were published by Jonna et al in Clinical Cancer Research.

The discovery represents an emerging field of research in which investigators focus on targetable genes responsible for the development of cancers, instead of focusing on the organ or body site in which the cancer appears. This approach is known as “tumor-agnostic” research.

“What all cancer researchers want is to find the right treatment for the right patient, regardless of where the tumor is. The future is to profile tumors in order to find unique vulnerabilities that can be treated with effective molecular therapy, and this research represents another step toward that goal,” said the study’s senior researcher, Stephen V. Liu, MD, Associate Professor of Medicine at Georgetown Lombardi Comprehensive Cancer Center. 

Study Findings

The NRG1 fusion occurs when the NRG1 gene, essential for normal development of the heart and nervous system, fuses together with another gene, such as CD74, a transmembrane protein often found on cancer cells. In this collaborative effort, the Caris Life Sciences’ molecular database was researched to describe the incidence and characterization of NRG1 fusions in solid tumors. 

This study defined the incidence of NRG1 fusions in almost 22,000 tumor specimens—the largest such study to date. Out of those nearly 22,000, 41 specimens harbored an NRG1 fusion (0.2%). The greatest incidence of NRG1 fusion was in non–small lung cancer (though this represented only 0.3% of all non­–small cell lung cancers), but the gene fusion, best found through RNA sequencing, was also found in kidney, gallbladder, bladder, ovarian, pancreatic, breast, and colorectal cancers, as well as in sarcoma and neuroendocrine cancers.

“Patients with these NRG1-linked cancers may derive less benefit from immunotherapy or usual treatments for site-specific cancers than they would receive from therapy that targets what is actually driving their cancer,” said Dr. Liu.

The researchers also found NRG1 fusion “partners”—proteins that bind with NRG1 proteins to make a pro-oncogenic pathway—are variable within and across tumor types.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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