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Genotype-phenotype correlations
Original research
Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma
  1. Jung Hee Kim1,
  2. Man Jin Kim2,
  3. Sung Hye Kong1,
  4. Su Jin Kim1,
  5. Hyein Kang3,
  6. Chan Soo Shin1,
  7. Sung Sup Park2,
  8. Kyu Eun Lee3,
  9. Moon-Woo Seong2
  1. 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  2. 2 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  3. 3 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  1. Correspondence to Professor Moon-Woo Seong, Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul 110-744, Korea (the Republic of); mwseong{at}snu.ac.kr

Abstract

Background Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing neuroendocrine tumours. PPGLs are a rare but important cause of secondary hypertension owing to their high morbidity and mortality. Patients with PPGL exhibit an increased prevalence of mutations in one of the PPGL susceptibility genes according to previous studies. We aimed to investigate the characteristics of germline mutations in the largest number of Korean patients with PPGL.

Methods In this study, 161 patients with PPGL were evaluated. Phenotype data, including biochemical, pathological and anatomical imaging results, were collected. Germline mutations in 10 PPGL-related genes were tested by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification.

Results Approximately 21% of apparently sporadic PPGLs harboured germline mutations of the PPGL-related genes. The mutation carriers were younger at the first diagnosis and had more bilateral (28.6% vs 4.0%, p<0.001) and multifocal (11.4% vs 1.6%, p=0.027) PPGLs, but showed no metastatic risk (17.1% vs 11.1%, p=0.504), than non-mutation carriers. Missense mutation of SDHD p.V111I was found in this cohort of Asian patients, which was associated with unilateral pheochromocytoma with dominantly epinephrine production.

Conclusion This study covered the largest number of Korean patients with PPGL. To our knowledge, it is the first to compare results of targeted NGS panel with those of conventional sequencing methods in Asia. We demonstrated that the variant type, as well as the mutated gene, may determine the phenotype and prognosis of PPGLs.

  • genetic testing
  • endocrine gland neoplasms
  • genetic heterogeneity

Data availability statement

Data are available upon reasonable request.

https://doi.org/10.1136/jmedgenet-2020-107102

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    Data availability statement

    Data are available upon reasonable request.

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    Footnotes

    • JHK and MJK contributed equally.

    • KEL and M-WS contributed equally.

    • Funding This study was supported by the Basic Science Research Program through the National Research Foundation of Korea by Grant NRF-2020R1A2C1014419.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.