Germline Mutations and Phenotypic Associations in Korean Patients With Pheochromocytoma and Paraganglioma: A Multicenter Study and Literature Review

Ann Lab Med. 2024 Nov 1;44(6):591-597. doi: 10.3343/alm.2023.0376. Epub 2024 Jul 29.

Abstract

Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype-phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype-phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies.

Keywords: Genotype; Germline; Korean; Paraganglioma; Phenotype; Pheochromocytoma.

Publication types

  • Review
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms* / diagnosis
  • Adrenal Gland Neoplasms* / genetics
  • Adrenal Gland Neoplasms* / pathology
  • Adult
  • Aged
  • East Asian People
  • Female
  • Genetic Association Studies
  • Genetic Testing
  • Germ-Line Mutation*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Male
  • Middle Aged
  • Neurofibromin 1 / genetics
  • Paraganglioma* / genetics
  • Paraganglioma* / pathology
  • Phenotype
  • Pheochromocytoma* / genetics
  • Pheochromocytoma* / pathology
  • Proto-Oncogene Proteins c-ret* / genetics
  • Republic of Korea
  • Succinate Dehydrogenase / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein* / genetics
  • Young Adult

Substances

  • Neurofibromin 1
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • SDHB protein, human
  • SDHD protein, human
  • Succinate Dehydrogenase
  • VHL protein, human
  • Von Hippel-Lindau Tumor Suppressor Protein