TY - JOUR
T1 - Clinical predictors and algorithm for the genetic diagnosis of pheochromocytoma patients
AU - Erlic, Zoran
AU - Rybicki, Lisa
AU - Peczkowska, Mariola
AU - Golcher, Henriette
AU - Kann, Peter H.
AU - Brauckhoff, Michael
AU - Müssig, Karsten
AU - Muresan, Michaela
AU - Schäffler, Andreas
AU - Reisch, Nicole
AU - Schott, Matthias
AU - Fassnacht, Martin
AU - Opocher, Giuseppe
AU - Klose, Silke
AU - Fottner, Christian
AU - Forrer, Flavio
AU - Plöckinger, Ursula
AU - Petersenn, Stephan
AU - Zabolotny, Dimitry
AU - Kollukch, Oleg
AU - Yaremchuk, Svetlana
AU - Januszewicz, Andrzej
AU - Walz, Martin K.
AU - Eng, Charis
AU - Neumann, Hartmut P H
PY - 2009/10/15
Y1 - 2009/10/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-09-1237
DO - 10.1158/1078-0432.CCR-09-1237
M3 - Article
C2 - 19825962
AN - SCOPUS:70350217774
VL - 15
SP - 6378
EP - 6385
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 20
ER -