Germline gene testing of the RET, VHL, SDHD and SDHB genes in patients with pheochromocytoma/paraganglioma.
- Author:
Kai WU
1
;
Yang ZHANG
1
;
Hong ZHANG
1
;
Zeng Huan TAN
2
;
Xiao Hui GUO
1
;
Jian Mei YANG
1
Author Information
1. Department of Endocrinology, Peking University First Hospital, Beijing 100034, China.
2. Department of Endocrinology, Handan Central Hospital, Handan 056001, Hebei, China.
- Publication Type:Journal Article
- MeSH:
Adrenal Gland Neoplasms/genetics*;
Genetic Testing;
Germ-Line Mutation;
Humans;
Paraganglioma/genetics*;
Pheochromocytoma/genetics*;
Proto-Oncogene Proteins c-ret/genetics*;
Succinate Dehydrogenase/genetics*;
Von Hippel-Lindau Tumor Suppressor Protein/genetics*
- From:
Journal of Peking University(Health Sciences)
2018;50(4):634-639
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the germline variations of genes RET, VHL, SDHD and SDHB in patients with pheochromocytoma and/or paraganglioma and to evaluate variations of these genes in Chinese patients.
METHODS:Patients who were treated in Peking University First Hospital from September 2012 to March 2014 and diagnosed with pheochromocytoma and/or paraganglioma by pathologists were included in this study. Twelve patients were included in total, of whom 11 had pheochromocytoma, and 1 had paraganglioma. Deoxyribonucleic acid (DNA) was extracted from the leukocytes of peripheral blood of the patients. The exons 10, 11, 13-16 of the RET gene, and all exons of VHL, SDHB and SDHD genes and their nearby introns (±20 bp) were amplified with polymerase chain reactions, and the products were sent to a biotechnology company for sequencing. The sequencing results were compared with wildtype sequences of these genes to identify variations. One of the patients was diagnosed with multiple endocrine neoplasia type 2A. A family analysis was performed in his kindred, and his family members received genetic tests for the related variations.
RESULTS:Three patients were found to have germline gene variations. A c.136C>T (p.R46X) variation of the SDHB gene was found in a patient with malignant pheochromocytoma. A c.1901G>A (C634Y) variation, as well as c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were found in a patient with multiple endocrine neoplasia type 2A. After a family analysis, five family members of this patient were found to have the same variations. c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene were also found in a clinical sporadic patient without evidence of malignancy. A patient with congenital single ventricle malformation and pheochromocytoma was included in this study, and no variation with clinical significance was found in the four genes of this patient.
CONCLUSION:25% (3/12) patients with pheochromocytoma or paraganglioma were found to have missense or nonsense germline gene variations in this study, including the c.136C>T (p.R46X) variation of the SDHB gene, the c.1901G>A (C634Y) variation of the RET gene, and c.2071G>A (p.G691S) and c.2712C>G (p.S904S) variations of the RET gene. The former two variations have already been confirmed to be pathogenic. The existence of these variations in Chinese patients with pheochromocytoma and/or paraganglioma was validated in this study, which supports the conclusion that genetic testing is necessary to be generally performed in patients with pheochromocytoma and/or paraganglioma.
