Detection of NRG1 gene fusions in solid tumors

Sushma Jonna, Rebecca A. Feldman, Jeffrey Swensen, Zoran Gatalica, Wolfgang M. Korn, Hossein Borghaei, Patrick C. Ma, Jorge J. Nieva, Alexander I. Spira, Vanderwalde Ari, Antoinette J. Wozniak, Edward S. Kim, Stephen V. Liu

Research output: Contribution to journalArticle

Abstract

Purpose: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. Experimental Design: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)–certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. Results: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non–small cell lung cancer (NSCLC, 25), though this represented only 0.3% of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. Conclusions: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner.

Original languageEnglish (US)
Pages (from-to)4966-4972
Number of pages7
JournalClinical Cancer Research
Volume25
Issue number16
DOIs
StatePublished - Aug 15 2019

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Gene Fusion
Neoplasms
Incidence
Breast Neoplasms
RNA Sequence Analysis
Gallbladder Neoplasms
Neuroendocrine Tumors
Gene Rearrangement
Sexual Partners
Multiplex Polymerase Chain Reaction
Genomics
Pancreatic Neoplasms
Renal Cell Carcinoma
Urinary Bladder Neoplasms
Non-Small Cell Lung Carcinoma
Sarcoma
Ovarian Neoplasms
Colorectal Neoplasms
Research Design
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jonna, S., Feldman, R. A., Swensen, J., Gatalica, Z., Korn, W. M., Borghaei, H., ... Liu, S. V. (2019). Detection of NRG1 gene fusions in solid tumors. Clinical Cancer Research, 25(16), 4966-4972. https://doi.org/10.1158/1078-0432.CCR-19-0160

Detection of NRG1 gene fusions in solid tumors. / Jonna, Sushma; Feldman, Rebecca A.; Swensen, Jeffrey; Gatalica, Zoran; Korn, Wolfgang M.; Borghaei, Hossein; Ma, Patrick C.; Nieva, Jorge J.; Spira, Alexander I.; Ari, Vanderwalde; Wozniak, Antoinette J.; Kim, Edward S.; Liu, Stephen V.

In: Clinical Cancer Research, Vol. 25, No. 16, 15.08.2019, p. 4966-4972.

Research output: Contribution to journalArticle

Jonna, S, Feldman, RA, Swensen, J, Gatalica, Z, Korn, WM, Borghaei, H, Ma, PC, Nieva, JJ, Spira, AI, Ari, V, Wozniak, AJ, Kim, ES & Liu, SV 2019, 'Detection of NRG1 gene fusions in solid tumors', Clinical Cancer Research, vol. 25, no. 16, pp. 4966-4972. https://doi.org/10.1158/1078-0432.CCR-19-0160
Jonna S, Feldman RA, Swensen J, Gatalica Z, Korn WM, Borghaei H et al. Detection of NRG1 gene fusions in solid tumors. Clinical Cancer Research. 2019 Aug 15;25(16):4966-4972. https://doi.org/10.1158/1078-0432.CCR-19-0160
Jonna, Sushma ; Feldman, Rebecca A. ; Swensen, Jeffrey ; Gatalica, Zoran ; Korn, Wolfgang M. ; Borghaei, Hossein ; Ma, Patrick C. ; Nieva, Jorge J. ; Spira, Alexander I. ; Ari, Vanderwalde ; Wozniak, Antoinette J. ; Kim, Edward S. ; Liu, Stephen V. / Detection of NRG1 gene fusions in solid tumors. In: Clinical Cancer Research. 2019 ; Vol. 25, No. 16. pp. 4966-4972.
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abstract = "Purpose: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. Experimental Design: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)–certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. Results: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2{\%}) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non–small cell lung cancer (NSCLC, 25), though this represented only 0.3{\%} of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. Conclusions: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner.",
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