Genetic Analysis and Clinical Characteristics of Hereditary Pheochromocytoma and Paraganglioma Syndrome in Korean Population.
Adolescent
Adrenal Gland Neoplasms
/ genetics
Adult
Aged
Child
Family
Female
Genetic Predisposition to Disease
Genetic Testing
/ methods
Germ-Line Mutation
/ genetics
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Paraganglioma
/ genetics
Pheochromocytoma
/ genetics
Republic of Korea
Young Adult
Genetic testing
Germ-line mutation
High-throughput nucleotide sequencing
Paraganglioma
Pheochromocytoma
Precision medicine
Journal
Endocrinology and metabolism (Seoul, Korea)
ISSN: 2093-5978
Titre abrégé: Endocrinol Metab (Seoul)
Pays: Korea (South)
ID NLM: 101554139
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
20
04
2020
accepted:
08
10
2020
entrez:
5
1
2021
pubmed:
6
1
2021
medline:
14
9
2021
Statut:
ppublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 33397040
pii: EnM.2020.683
doi: 10.3803/EnM.2020.683
pmc: PMC7803615
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
858-872Subventions
Organisme : Korea Health Industry Development Institute
Pays : International
Organisme : Ministry of Health and Welfare
ID : HI19C0189
Pays : International
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