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RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.

Publication ,  Journal Article
Severson, E; Achyut, BR; Nesline, M; Pabla, S; Previs, RA; Kannan, G; Chenn, A; Zhang, S; Klein, R; Conroy, J; Sausen, M; Sathyan, P ...
Published in: J Mol Diagn
July 2023

NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4397 solid tumor formalin-fixed, paraffin-embedded samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen NRG1 fusions were found in 17 unique patients, across multiple tumor types, including non-small-cell lung (n = 7), breast (n = 2), colorectal (n = 3), esophageal (n = 2), ovarian (n = 1), pancreatic (n = 1), and unknown primary (n = 1) carcinomas, with a cumulative incidence of 0.38%. Fusions were identified with breakpoints across four NRG1 introns spanning 1.4 megabases, with a mixture of known (n = 8) and previously unreported (n = 11) fusion partners. Co-occurring driver alterations in tumors with NRG1 fusions were uncommon, except colorectal carcinoma, where concurrent alterations in APC, BRAF, and ERBB2 were present in a subset of cases. The overall lack of co-occurring drivers highlights the importance of identifying NRG1 gene fusions, as these patients are unlikely to harbor other targetable alterations. In addition, RNA sequencing is important to identify NRG1 gene fusions given the variety of fusion partners and large genomic areas where breakpoints can occur.

Duke Scholars

Published In

J Mol Diagn

DOI

EISSN

1943-7811

Publication Date

July 2023

Volume

25

Issue

7

Start / End Page

454 / 466

Location

United States

Related Subject Headings

  • Sequence Analysis, RNA
  • Pathology
  • Oncogene Proteins, Fusion
  • Neuregulin-1
  • Lung Neoplasms
  • Humans
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma
  • Base Sequence
  • 3211 Oncology and carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
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Severson, E., Achyut, B. R., Nesline, M., Pabla, S., Previs, R. A., Kannan, G., … Ramkissoon, S. H. (2023). RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers. J Mol Diagn, 25(7), 454–466. https://doi.org/10.1016/j.jmoldx.2023.03.011
Severson, Eric, Bhagelu R. Achyut, Mary Nesline, Sarabjot Pabla, Rebecca A. Previs, Geoffrey Kannan, Anjen Chenn, et al. “RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.J Mol Diagn 25, no. 7 (July 2023): 454–66. https://doi.org/10.1016/j.jmoldx.2023.03.011.
Severson E, Achyut BR, Nesline M, Pabla S, Previs RA, Kannan G, et al. RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers. J Mol Diagn. 2023 Jul;25(7):454–66.
Severson, Eric, et al. “RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.J Mol Diagn, vol. 25, no. 7, July 2023, pp. 454–66. Pubmed, doi:10.1016/j.jmoldx.2023.03.011.
Severson E, Achyut BR, Nesline M, Pabla S, Previs RA, Kannan G, Chenn A, Zhang S, Klein R, Conroy J, Sausen M, Sathyan P, Saini KS, Ghosh A, Jensen TJ, Reddy P, Ramkissoon SH. RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers. J Mol Diagn. 2023 Jul;25(7):454–466.
Journal cover image

Published In

J Mol Diagn

DOI

EISSN

1943-7811

Publication Date

July 2023

Volume

25

Issue

7

Start / End Page

454 / 466

Location

United States

Related Subject Headings

  • Sequence Analysis, RNA
  • Pathology
  • Oncogene Proteins, Fusion
  • Neuregulin-1
  • Lung Neoplasms
  • Humans
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma
  • Base Sequence
  • 3211 Oncology and carcinogenesis