Background@#
Pheochromocytoma and
paragangliomas (PPGL) are hereditary in approximately 30% to 40% cases. With the advancement of genetic
analysis techniques, including
next-generation sequencing (NGS), there were attempts to classify PPGL into molecular clusters. With NGS being applied to clinical settings recently, we aimed to
review the results of genetic
analysis, including NGS, and investigate the
association with clinical characteristics in Korean PPGL
patients. @*
Methods@#We reviewed the
medical records of PPGL
patients who visited Severance
hospital from 2006 to 2019. We documented the clinical
phenotype of those
who underwent targeted NGS or had known
germline mutations of related
genes. @*Results@#Among 57 PPGL
patients, we found 28 pathogenic
germline mutations of susceptibility
genes. Before the targeted NGS was implemented, only obvious syndromic feature
lead to the Sanger sequencing for the specific
genes. Therefore, for the exact
prevalence, only
patients after the year 2017, when targeted NGS was added, were included (n=43). The positive
germline mutations were found in 14
patients; thus, the
incidence rate is 32.6%.
Patients with
germline mutations had a higher likelihood of
family history. There were significant differences in the type of PPGLs, percentage of
family history,
metastasis rate, presence of other
tumors, and biochemical profile among three molecular clusters pseudohypoxic
tricarboxylic acid cycle-related, pseudohypoxic von Hippel-Lindau (
VHL)/endothelial PAS domain-containing
protein 1-related, and
kinase-signaling group.
Germline mutations were identified in seven PPGL-related
genes (SDHB, RET,
VHL, NF1, MAX, SDHA, and SDHD). @*Conclusion@#We
report the expected
prevalence of
germline mutations in Korean PPGL
patients. NGS is a useful and accessible tool for genetic
analysis in
patients with PPGLs, and further
research on molecular
classification is needed for precise management.