Oncotarget

Research Papers:

Phenylethanolamine N-methyltransferase downregulation is associated with malignant pheochromocytoma/paraganglioma

Seung Eun Lee, Ensel Oh, Boram Lee, Yu Jin Kim, Doo-Yi Oh, Kyungsoo Jung, Jong-Sun Choi, Junghan Kim, Sung Joo Kim, Jung Wook Yang, Jungsuk An, Young Lyun Oh and Yoon-La Choi _

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Oncotarget. 2016; 7:24141-24153. https://doi.org/10.18632/oncotarget.8234

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Abstract

Seung Eun Lee1,*, Ensel Oh3,4,*, Boram Lee2, Yu Jin Kim3, Doo-Yi Oh3,4, Kyungsoo Jung3,4, Jong-Sun Choi5, Junghan Kim6, Sung Joo Kim6, Jung Wook Yang7, Jungsuk An8, Young Lyun Oh2, Yoon-La Choi2,3,4

1Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea

2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

3Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea

5The Center for Anti-Cancer Companion Diagnostics, School of Biological Science, Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul, Korea

6Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

7Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea

8Department of Pathology, Gachon University Gil Medical Center, Incheon, Korea

*These authors contributed equally to this work

Correspondence to:

Yoon-La Choi, e-mail: ylachoi@skku.edu

Young Lyun Oh, e-mail: yl.oh@samsung.com

Keywords: pheochromocytoma/paraganglioma, phenylethanolamine N-methyltransferase, biomarker, metastasis, endocrine tumors

Received: May 22, 2015     Accepted: February 10, 2016     Published: March 21, 2016

ABSTRACT

Malignant pheochromocytoma/paraganglioma (PCC/PGL) is defined by the presence of metastases at non-chromaffin sites, which makes it difficult to prospectively diagnose malignancy. Here, we performed array CGH (aCGH) and paired gene expression profiling of fresh, frozen PCC/PGL samples (n = 12), including three malignant tumors, to identify genes that distinguish benign from malignant tumors. Most PCC/PGL cases showed few copy number aberrations, regardless of malignancy status, but mRNA analysis revealed that 390 genes were differentially expressed in benign and malignant tumors. Expression of the enzyme, phenylethanolamine N-methyltransferase (PNMT), which catalyzes the methylation of norepinephrine to epinephrine, was significantly lower in malignant PCC/PGL as compared to benign samples. In 62 additional samples, we confirmed that PNMT mRNA and protein levels were decreased in malignant PCC/PGL using quantitative real-time polymerase chain reaction and immunohistochemistry. The present study demonstrates that PNMT downregulation correlates with malignancy in PCC/PGL and identifies PNMT as one of the most differentially expressed genes between malignant and benign tumors.


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