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Published on: May 17, 2024
Familial nonsyndromic pheochromocytoma
Giuseppe Opocher1, Francesca Schiavi, Maurizio Iacobone
1Endocrinology Unit, Department of Medical and Surgical Sciences, University Hospital of Padova, Padova, Italy. giuseppe.opocher@nipd.it
Genetic testing identified familial pheochromocytoma cases lacking mutations in known susceptibility genes like RET and VHL. This suggests the existence of undiscovered genes contributing to pheochromocytoma development.
Area of Science:
- Endocrinology
- Human Genetics
- Oncology
Background:
- Heritable pheochromocytomas constitute 30-40% of cases.
- Known genetic drivers include germline mutations in VHL, RET, SDHB, and SDHD genes.
- The molecular basis for familial pheochromocytoma is partially understood.
Purpose of the Study:
- To investigate the genetic underpinnings of familial pheochromocytoma.
- To identify novel susceptibility genes beyond the established RET, VHL, SDHB, SDHC, SDHD, and EGLN3 genes.
- To analyze a cohort of 172 sporadic and familial pheochromocytomas.
Main Methods:
- Genotyping of 172 pheochromocytoma samples.
- Sequence analysis of RET (exons 8, 10, 11, 13, 14, 15, 16).
- Full coding sequence and exon-intron boundary analysis of VHL, SDHB, SDHC, SDHD, and EGLN3 genes.
Main Results:
- Four unrelated families with familial pheochromocytoma showed no sequence variants in RET, VHL, SDHB, SDHC, SDHD, or EGLN3.
- One family (Family 4) presented a VHL sequence variant (IVS2+43 A>G) also found in a sporadic case.
- Family 3 exhibited a history of pheochromocytoma, breast cancer, laryngeal cancer, leukemia, and medullary thyroid carcinoma.
Conclusions:
- The identified families with pheochromocytoma lacking mutations in known genes suggest the involvement of other, yet undiscovered, susceptibility genes.
- Further research is warranted to elucidate the complete genetic landscape of familial pheochromocytoma.
- The findings highlight the complexity of hereditary pheochromocytoma beyond currently identified mutations.
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