Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients

Zoran Erlic, Lisa Rybicki, Mariola Peczkowska, Henriette Golcher, Peter H. Kann, Michael Brauckhoff, Karsten Müssig, Michaela Muresan, Andreas Schäffler, Nicole Reisch, Matthias Schott, Martin Fassnacht, Giuseppe Opocher, Silke Klose, Christian Fottner, Flavio Forrer, Ursula Plöckinger, Stephan Petersenn, Dimitry Zabolotny, Oleg KollukchSvetlana Yaremchuk, Andrzej Januszewicz, Martin K. Walz, Charis Eng, Hartmut P H Neumann

Research output: Contribution to journalArticlepeer-review


Purpose: Six pheochromocytoma susceptibility genes causing distinct syndromes have been identified; approximately one of three of all pheochromocytoma patients carry a predisposing germline mutation. When four major genes (VHL, RET, SDHB, SDHD) are analyzed in a clinical laboratory, costs are ∼$3,400 per patient. The aim of the study is to systematically obtain a robust algorithm to identify who should be genetically tested, and to determine the order in which genes should be tested. Experimental Design: DNA from 989 apparently nonsyndromic patients were scanned for germline mutations in the genes VHL, RET, SDHB, SDHC, and SDHD. Clinical parameters were analyzed as potential predictors for finding mutations by multiple logistic regression, validated by bootstrapping. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Results: Of 989 apparently nonsyndromic pheochromocytoma cases, 187 (19%) harbored germline mutations. Predictors for presence of mutation are age SDHB>RET>VHL. Using the clinical predictor algorithm to prioritize gene testing and order, a 44.7% cost reduction in diagnostic process can be achieved. Conclusions: Clinical parameters can predict for mutation carriers and help prioritize gene testing to reduce costs in nonsyndromic pheochromocytoma presentations.

Original languageEnglish
Pages (from-to)6378-6385
Number of pages8
JournalClinical Cancer Research
Issue number20
Publication statusPublished - Oct 15 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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