Endocrine

, Volume 59, Issue 1, pp 175–182 | Cite as

Routine genetic screening with a multi-gene panel in patients with pheochromocytomas

  • Emilia Sbardella
  • Treena Cranston
  • Andrea M. Isidori
  • Brian Shine
  • Aparna Pal
  • Bahram Jafar-Mohammadi
  • Greg Sadler
  • Radu Mihai
  • Ashley B. Grossman
Original Article

Abstract

Purpose

Several new gene mutations have been reported in recent years to be associated with a risk of familial pheochromocytoma. However, it is unclear as to whether extensive genetic testing is required in all patients.

Methods

The clinical data of consecutive patients operated for pheochromocytoma over a decade in a tertiary referral center were reviewed. Genetic screening was performed using a 10-gene panel: RET, VHL, SDHB, SDHD, SDHA, SDHC, SDHAF2, MAX, TMEM127 and FH.

Results

A total of 166 patients were analyzed: 87 of them had genetic screening performed (39 M: 44.8%, 48 F: 55.2%, age range 6–81 years, mean 45±16.8 years). In total, 22/87 (25.3%) patients had germline mutations, while 65/87 (74.7%) patients presented with apparently sporadic tumors. Germline VHL mutations were identified in 11.7% of patients, RET in 6.8% (five MEN2A/MEN2 and one MEN2B/MEN3), SDHD in 2.3%, MAX in 2.3%, SDHB in 1.1%, and TMEM127 in 1.1% of patients. At diagnosis, 15.1% of patients with unilateral non-syndromic pheochromocytoma showed germline mutations. We identified 19.7% of mutations in patients with unilateral-non-recurrent pheochromocytomas within 5 years vs. 50% in the recurrent-bilateral-metastatic group (p = 0.01). Germline mutations were more frequently seen with bilateral pheochromocytomas (p = 0.001): 80% of patients with bilateral disease had germline mutations (4 VHL, 3 RET, 1 MAX).

Conclusions

The advent of rapid genetic screening using a gene-panel makes it feasible to screen large cohorts of patients and provides a valuable tool to contribute to the prediction of bilateral and malignant disease and to screen family members.

Keywords

Pheochromocytoma Gene Genetic screening Adrenal Sporadic 

Abbreviations

PHEO

Pheochromocytomas

PGL

Paraganglioma

NET

Neuroendocrine tumor

NMA

Normetanephrines

MA

Metanephrines

3MT

3-methoxythyramine

NGS

Next-generationsequencing

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration, and its later amendments or comparable ethical standards.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill HospitalUniversity of OxfordOxfordUK
  2. 2.Department of Experimental MedicineSapienza University of RomeRomeItaly
  3. 3.Oxford Medical Genetics Laboratories, Churchill HospitalUniversity of OxfordOxfordUK
  4. 4.Department of Clinical Biochemistry,John Radcliffe HospitalUniversity of OxfordOxfordUK
  5. 5.Department of Endocrine Surgery, Churchill HospitalOxford University Hospitals NHS Foundation TrustOxfordUK

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