Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions PMID: 29084941

ADC Targets in Oncology

2026-04-10

Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions

Nat Commun. 2017 Oct 30;8(1):1197. doi: 10.1038/s41467-017-01178-z.

Martin G Dalin ¹ ² ³ , Nora Katabi ⁴ , Marta Persson ⁵ , Ken-Wing Lee ¹ , Vladimir Makarov ¹ ⁶ , Alexis Desrichard ¹ ⁶ , Logan A Walsh ¹ , Lyndsay West ⁷ , Zaineb Nadeem ¹ ⁷ , Deepa Ramaswami ¹ ⁷ , Jonathan J Havel ¹ ⁶ , Fengshen Kuo ¹ ⁶ , Kalyani Chadalavada ⁸ , Gouri J Nanjangud ⁸ , Ian Ganly ⁷ , Nadeem Riaz ⁶ ⁹ , Alan L Ho ¹⁰ , Cristina R Antonescu ⁴ , Ronald Ghossein ⁴ , Göran Stenman ⁵ , Timothy A Chan ¹¹ ¹² ¹³ , Luc G T Morris ¹⁴ ¹⁵ ¹⁶

Affiliations

1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
2. Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, 41685, Gothenburg, Sweden.
3. Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 41685, Gothenburg, Sweden.
4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
5. Sahlgrenska Cancer Center, Department of Pathology and Genetics, University of Gothenburg, 40530, Gothenburg, Sweden.
6. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
7. Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
8. Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
9. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
10. Head and Neck Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
11. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].
12. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].
13. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].
14. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].
15. Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].
16. Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. [email protected].

Abstract

Myoepithelial carcinoma (MECA) is an aggressive salivary gland Cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 Other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal Cancer.