Neumann, Hartmut P. H. and Erlic, Zoran and Boedeker, Carsten C. and Rybicki, Lisa A. and Robledo, Mercedes and Hermsen, Mario and Schiavi, Francesca and Falcioni, Maurizio and Kwok, Pingling and Bauters, Catherine and Lampe, Karen and Fischer, Markus and Edelman, Emily and Benn, Diana E. and Robinson, Bruce G. and Wiegand, Stefanie and Rasp, Gerd and Stuck, Boris A. and Hoffmann, Michael M. and Sullivan, Maren and Sevilla, Maria A. and Weiss, Marjan M. and Peczkowska, Mariola and Kubaszek, Agata and Pigny, Pascal and Ward, Robyn L. and Learoyd, Diana and Croxson, Michael and Zabolotny, Dmitry and Yaremchuk, Svetlana and Draf, Wolfgang and Muresan, Mihaela and Lorenz, Robert R. and Knipping, Stephan and Strohm, Michael and Dyckhoff, Gerhard and Matthias, Christoph and Reisch, Nicole and Preuss, Simon F. and Esser, Dirk and Walter, Martin A. and Kaftan, Holger and Stoever, Timo and Fottner, Christian and Gorgulla, Harald and Malekpour, Mahdi and Zarandy, Masoud Motasaddi and Schipper, Joerg and Brase, Christoph and Glien, Alexander and Kuehnemund, Matthias and Koscielny, Sven and Schwerdtfeger, Peter and Valimaki, Matti and Szyfter, Witold and Finckh, Ulrich and Zerres, Klaus and Cascon, Alberto and Opocher, Giuseppe and Ridder, Gerd J. and Januszewicz, Andrzej and Suarez, Carlos and Eng, Charis (2009) Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out. CANCER RESEARCH, 69 (8). pp. 3650-3656. ISSN 0008-5472,
Full text not available from this repository. (Request a copy)Abstract
Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs similar to US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age <= 40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction cam be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care. [Cancer Res 2009;69(8):3650-6]
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CAROTID-BODY PARAGANGLIOMA; VONHIPPEL-LINDAU DISEASE; SDHD GENE; HEREDITARY PARAGANGLIOMA; FAMILIAL PARAGANGLIOMA; MATERNAL TRANSMISSION; LINE MUTATIONS; PHEOCHROMOCYTOMA; SUSCEPTIBILITY; PREVALENCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Hals-Nasen-Ohren-Heilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Sep 2020 12:36 |
| Last Modified: | 17 Sep 2020 12:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29122 |
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