# Germline mutations in nonsyndromic pheochromocytoma

Source: https://onco.cc/key-papers/paper-neumann-germline-mutations-nonsyndromic-pheochromocytoma-nejm-2002/  
OnCo record `paper-neumann-germline-mutations-nonsyndromic-pheochromocytoma-nejm-2002` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

One in four patients with an apparently sporadic adrenaline-producing tumour turned out to carry an inherited mutation in one of four genes, showing that pheochromocytoma is the most heritable of all tumours and that everyone with one should be offered genetic testing.

## Summary

Study of 271 patients with pheochromocytoma or paraganglioma and no family history or syndromic features, from the Freiburg-Warsaw-Columbus registry, tested for germline mutations in VHL, RET, SDHD and SDHB.

Mutations were found in 66 patients (24 percent), most often in VHL and SDHB, and were associated with younger age, multifocal and extra-adrenal tumours. The finding transformed pheochromocytoma from a tumour with 10 percent heritability to one where germline testing is recommended for every patient.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: New England Journal of Medicine
- Year: 2002
- DOI: 10.1056/NEJMoa020152
- Authors: Neumann HP, Bausch B, McWhinney SR, et al.
- Findings: Germline mutations in VHL, RET, SDHD or SDHB in 66 of 271 (24 percent) apparently sporadic cases.; Mutation carriers were younger and more often had multifocal or extra-adrenal tumours.
- What it means: Every patient with a pheochromocytoma or paraganglioma is now offered germline testing, which directs surveillance of the patient and relatives and, with SDHB, warns of metastatic risk.
- Caveats: Only four genes were tested; more than a dozen susceptibility genes are now known, raising the heritable fraction to about 40 percent.; Registry population may over-represent younger patients.

## Sources

- N Engl J Med 2002: https://doi.org/10.1056/NEJMoa020152
- PubMed: https://pubmed.ncbi.nlm.nih.gov/12000816/

## Connected records

- cancers: [Hereditary pheochromocytoma and paraganglioma (SDHx, VHL, RET, NF1, MAX and TMEM127)](https://onco.cc/cancers/hereditary-ppgl/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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