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

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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.

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Abbreviations

PHEO:

Pheochromocytomas

PGL:

Paraganglioma

NET:

Neuroendocrine tumor

NMA:

Normetanephrines

MA:

Metanephrines

3MT:

3-methoxythyramine

NGS:

Next-generationsequencing

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Authors and Affiliations

  1. Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK, OX3 7LE, UK

    Emilia Sbardella, Aparna Pal, Bahram Jafar-Mohammadi & Ashley B. Grossman

  2. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, Rome, 00161, Italy

    Emilia Sbardella & Andrea M. Isidori

  3. Oxford Medical Genetics Laboratories, Churchill Hospital, University of Oxford, Oxford, UK, OX3 7LE, UK

    Treena Cranston

  4. Department of Clinical Biochemistry,John Radcliffe Hospital, University of Oxford, Oxford, UK, OX3 9DU, UK

    Brian Shine

  5. Department of Endocrine Surgery, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, OX3 7LE, UK

    Greg Sadler & Radu Mihai

Authors
  1. Emilia Sbardella
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  2. Treena Cranston
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  3. Andrea M. Isidori
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  4. Brian Shine
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  9. Ashley B. Grossman
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Correspondence to Emilia Sbardella.

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The authors declare that they have no competing interests.

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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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Sbardella, E., Cranston, T., Isidori, A.M. et al. Routine genetic screening with a multi-gene panel in patients with pheochromocytomas. Endocrine 59, 175–182 (2018). https://doi.org/10.1007/s12020-017-1310-9

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  • DOI: https://doi.org/10.1007/s12020-017-1310-9

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