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Case Reports
. 2024 Nov 6:14:1472725.
doi: 10.3389/fonc.2024.1472725. eCollection 2024.

Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis

Anthony Crymes  1 , Mark G Evans  2 , Tolulope Adeyelu  3 , Jack Reid  4 , Ifegwu O Ibe  5 , Matthew J Oberley  2 , Jill H Tseng  6
Affiliations
Case Reports

Case report: High grade serous fallopian tube carcinoma with rare NRG1 gene fusion presenting as widespread peritoneal carcinomatosis

Anthony Crymes et al. Front Oncol. .

Abstract

The discovery of gene fusions involving Neuregulin-1 (NRG1) within solid tumors has important therapeutic implications, as they are being actively explored as targets for emerging ERBB/ERBB2/ERBB3-directed anti-cancer agents. NRG1 fusions are very uncommon across all tumor types and are infrequently documented in the medical literature. We report a female patient presenting with widespread peritoneal carcinomatosis diagnosed as high grade serous fallopian tube carcinoma, which harbored a previously undescribed MYH10::NRG1 fusion. Moreover, we queried the whole transcriptome sequencing results of neoplasms analyzed by a commercial laboratory (Caris Life Sciences) to determine the overall incidence of NRG1 fusions in carcinomas of the ovary, fallopian tube, and peritoneum (0.18%). Twenty-five additional tumors were found to demonstrate NRG1 fusions, including 20 new genes partners that had not been previously identified in gynecologic carcinomas. Overall, NRG1 fusion events are rare in ovarian, fallopian tube, and primary peritoneal carcinomas, but they may carry diagnostic significance in the context of borderline/low grade serous tumors, which demonstrated exclusively CLU::NRG1 fusions, and could have important predictive implications for response to ERBB/ERBB2/ERBB3-directed therapies.

Keywords: NRG1 gene fusion; fallopian tube cancer; ovarian cancer; primary peritoneal cancer; serous carcinoma.

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Conflict of interest statement

TA, MO, and ME disclose a financial association with Caris Life Sciences full-time employment, travel/speaking expenses, stock/stock options. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Gene Set Enrichment Analysis (GSEA) results of NRG1 fusion-positive tumor cases compared to low grade serous carcinomas of the female genital tract. Asterisks indicate statistically significance differences (p-value <0.05).
Figure 2
Figure 2
Hematoxylin and eosin-stained high grade serous carcinoma metastatic to pleural fluid harboring a MYH10 exon 3::NRG1 exon 2 fusion (400x magnification, (A); a pictorial representation of the MYH10::NRG1 gene fusion, which includes the intact immunoglobulin and EGF domains of NRG1. Ex, exon (B).
Figure 3
Figure 3
CT chest, abdomen, and pelvis imaging that reveals a right-sided pleural effusion and widespread peritoneal carcinomatosis (arrows).
Figure 4
Figure 4
Patient’s treatment timeline for management of Stage IV high grade serous fallopian tube carcinoma.
See this image and copyright information in PMC

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References

    1. Steinthorsdottir V, Stefansson H, Ghosh S, Birgisdottir B, Bjornsdottir S, Fasquel AC, et al. . Multiple novel transcription initiation sites for NRG1. Gene. (2004) 342:97–105. doi: 10.1016/j.gene.2004.07.029 - DOI - PubMed
    1. Fernandez-Cuesta L, Thomas RK. Molecular pathways: targeting NRG1 fusions in lung cancer. Clin Cancer Res. (2015) 21:1989–94. doi: 10.1158/1078-0432.CCR-14-0854 - DOI - PubMed
    1. Jonna S, Feldman RA, Swensen J, Gatalica Z, Korn WM, Borghaei H, et al. . Detection of NRG1 gene fusions in solid tumors. Clin Cancer Res. (2019) 25:4966–72. doi: 10.1158/1078-0432.CCR-19-0160 - DOI - PMC - PubMed
    1. Nagasaka M, Ou SI. NRG1 and NRG2 fusion positive solid tumor Malignancies: a paradigm of ligand-fusion oncogenesis. Trends Cancer. (2022) 8:242–58. doi: 10.1016/j.trecan.2021.11.003 - DOI - PubMed
    1. 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) 25:454–66. doi: 10.1016/j.jmoldx.2023.03.011 - DOI - PubMed

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