Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out

Hartmut P. H Neumann, Zoran Erlic, Carsten C Boedeker, Lisa A Rybicki, Mercedes Robledo, Mario Hermsen, Francesca Schiavi, Maurizio Falcioni, Pingling Kwok, Catherine Bauters, Karen Lampe, Markus Fischer, Emily Edelman, Diana E Benn, Bruce G Robinson, Stefanie Wiegand, Gerd Rasp, Boris A Stuck, Michael M Hoffmann, Maren SullivanMaria A Sevilla, Marjan M Weiss, Mariola Peczkowska, Agata Kubaszek, Pascal Pigny, Robyn L Ward, Diana Learoyd, Michael Croxson, Dmitry Zabolotny, Svetlana Yaremchuk, Wolfgang Draf, Mihaela Muresan, Robert R Lorenz, Stephan Knipping, Michael Strohm, Gerhard Dyckhoff, Christoph Matthias, Nicole Reisch, Simon F Preuss, Dirk Eßer, Martin A Walter, Holger Kaftan, Timo Stöver, Christian Fottner, Harald Gorgulla, Mahdi Malekpour, Masoud Motasaddi Zarandy, Jörg Schipper, Christoph Brase, Alexander Glien, Matthias Kuhnemund, Sven Koscielny, Peter Schwerdtfeger, Matti Välimäki, Witold Szyfter, Ulrich Finckh, Klaus Zerres, Alberto Cascon, Giuseppe Opocher, Gerd J Ridder, Andrzej Januszewicz, Carlos Suarez, Charis Eng

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    "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]"
    Originalspråkengelska
    TidskriftCancer Research
    Volym69
    Sidor (från-till)3650-3656
    Antal sidor7
    ISSN0008-5472
    DOI
    StatusPublicerad - 2009
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Neumann, Hartmut P. H ; Erlic, Zoran ; Boedeker, Carsten C ; Rybicki, Lisa A ; Robledo, Mercedes ; Hermsen, Mario ; Schiavi, Francesca ; Falcioni, Maurizio ; Kwok, Pingling ; Bauters, Catherine ; Lampe, Karen ; Fischer, Markus ; Edelman, Emily ; Benn, Diana E ; Robinson, Bruce G ; Wiegand, Stefanie ; Rasp, Gerd ; Stuck, Boris A ; Hoffmann, Michael M ; Sullivan, Maren ; Sevilla, Maria A ; Weiss, Marjan M ; Peczkowska, Mariola ; Kubaszek, Agata ; Pigny, Pascal ; Ward, Robyn L ; Learoyd, Diana ; Croxson, Michael ; Zabolotny, Dmitry ; Yaremchuk, Svetlana ; Draf, Wolfgang ; Muresan, Mihaela ; Lorenz, Robert R ; Knipping, Stephan ; Strohm, Michael ; Dyckhoff, Gerhard ; Matthias, Christoph ; Reisch, Nicole ; Preuss, Simon F ; Eßer, Dirk ; Walter, Martin A ; Kaftan, Holger ; Stöver, Timo ; Fottner, Christian ; Gorgulla, Harald ; Malekpour, Mahdi ; Zarandy, Masoud Motasaddi ; Schipper, Jörg ; Brase, Christoph ; Glien, Alexander ; Kuhnemund, Matthias ; Koscielny, Sven ; Schwerdtfeger, Peter ; Välimäki, Matti ; Szyfter, Witold ; Finckh, Ulrich ; Zerres, Klaus ; Cascon, Alberto ; Opocher, Giuseppe ; Ridder, Gerd J ; Januszewicz, Andrzej ; Suarez, Carlos ; Eng, Charis. / Clinical predictors for germline mutations in head and neck paraganglioma patients : cost reduction strategy in genetic diagnostic process as fall-out. I: Cancer Research. 2009 ; Vol. 69. s. 3650-3656.
    @article{c6174c537e3049cabeb909cfd720668f,
    title = "Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out",
    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]{"}",
    author = "Neumann, {Hartmut P. H} and Zoran Erlic and Boedeker, {Carsten C} and Rybicki, {Lisa A} and Mercedes Robledo and Mario Hermsen and Francesca Schiavi and Maurizio Falcioni and Pingling Kwok and Catherine Bauters and Karen Lampe and Markus Fischer and Emily Edelman and Benn, {Diana E} and Robinson, {Bruce G} and Stefanie Wiegand and Gerd Rasp and Stuck, {Boris A} and Hoffmann, {Michael M} and Maren Sullivan and Sevilla, {Maria A} and Weiss, {Marjan M} and Mariola Peczkowska and Agata Kubaszek and Pascal Pigny and Ward, {Robyn L} and Diana Learoyd and Michael Croxson and Dmitry Zabolotny and Svetlana Yaremchuk and Wolfgang Draf and Mihaela Muresan and Lorenz, {Robert R} and Stephan Knipping and Michael Strohm and Gerhard Dyckhoff and Christoph Matthias and Nicole Reisch and Preuss, {Simon F} and Dirk E{\ss}er and Walter, {Martin A} and Holger Kaftan and Timo St{\"o}ver and Christian Fottner and Harald Gorgulla and Mahdi Malekpour and Zarandy, {Masoud Motasaddi} and J{\"o}rg Schipper and Christoph Brase and Alexander Glien and Matthias Kuhnemund and Sven Koscielny and Peter Schwerdtfeger and Matti V{\"a}lim{\"a}ki and Witold Szyfter and Ulrich Finckh and Klaus Zerres and Alberto Cascon and Giuseppe Opocher and Ridder, {Gerd J} and Andrzej Januszewicz and Carlos Suarez and Charis Eng",
    year = "2009",
    doi = "10.1158/0008-5472.CAN-08-4057",
    language = "English",
    volume = "69",
    pages = "3650--3656",
    journal = "Cancer Research",
    issn = "0008-5472",
    publisher = "American Association for Cancer Research",

    }

    Neumann, HPH, Erlic, Z, Boedeker, CC, Rybicki, LA, Robledo, M, Hermsen, M, Schiavi, F, Falcioni, M, Kwok, P, Bauters, C, Lampe, K, Fischer, M, Edelman, E, Benn, DE, Robinson, BG, Wiegand, S, Rasp, G, Stuck, BA, Hoffmann, MM, Sullivan, M, Sevilla, MA, Weiss, MM, Peczkowska, M, Kubaszek, A, Pigny, P, Ward, RL, Learoyd, D, Croxson, M, Zabolotny, D, Yaremchuk, S, Draf, W, Muresan, M, Lorenz, RR, Knipping, S, Strohm, M, Dyckhoff, G, Matthias, C, Reisch, N, Preuss, SF, Eßer, D, Walter, MA, Kaftan, H, Stöver, T, Fottner, C, Gorgulla, H, Malekpour, M, Zarandy, MM, Schipper, J, Brase, C, Glien, A, Kuhnemund, M, Koscielny, S, Schwerdtfeger, P, Välimäki, M, Szyfter, W, Finckh, U, Zerres, K, Cascon, A, Opocher, G, Ridder, GJ, Januszewicz, A, Suarez, C & Eng, C 2009, 'Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out', Cancer Research, vol. 69, s. 3650-3656. https://doi.org/10.1158/0008-5472.CAN-08-4057

    Clinical predictors for germline mutations in head and neck paraganglioma patients : cost reduction strategy in genetic diagnostic process as fall-out. / Neumann, Hartmut P. H; Erlic, Zoran; Boedeker, Carsten C; Rybicki, Lisa A; Robledo, Mercedes; Hermsen, Mario; Schiavi, Francesca; Falcioni, Maurizio; Kwok, Pingling; Bauters, Catherine; Lampe, Karen; Fischer, Markus; Edelman, Emily; Benn, Diana E; Robinson, Bruce G; Wiegand, Stefanie; Rasp, Gerd; Stuck, Boris A; Hoffmann, Michael M; Sullivan, Maren; Sevilla, Maria A; Weiss, Marjan M; Peczkowska, Mariola; Kubaszek, Agata; Pigny, Pascal; Ward, Robyn L; Learoyd, Diana; Croxson, Michael; Zabolotny, Dmitry; Yaremchuk, Svetlana; Draf, Wolfgang; Muresan, Mihaela; Lorenz, Robert R; Knipping, Stephan; Strohm, Michael; Dyckhoff, Gerhard; Matthias, Christoph; Reisch, Nicole; Preuss, Simon F; Eßer, Dirk; Walter, Martin A; Kaftan, Holger; Stöver, Timo; Fottner, Christian; Gorgulla, Harald; Malekpour, Mahdi; Zarandy, Masoud Motasaddi; Schipper, Jörg; Brase, Christoph; Glien, Alexander; Kuhnemund, Matthias; Koscielny, Sven; Schwerdtfeger, Peter; Välimäki, Matti; Szyfter, Witold; Finckh, Ulrich; Zerres, Klaus; Cascon, Alberto; Opocher, Giuseppe; Ridder, Gerd J; Januszewicz, Andrzej; Suarez, Carlos; Eng, Charis.

    I: Cancer Research, Vol. 69, 2009, s. 3650-3656.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Clinical predictors for germline mutations in head and neck paraganglioma patients

    T2 - cost reduction strategy in genetic diagnostic process as fall-out

    AU - Neumann, Hartmut P. H

    AU - Erlic, Zoran

    AU - Boedeker, Carsten C

    AU - Rybicki, Lisa A

    AU - Robledo, Mercedes

    AU - Hermsen, Mario

    AU - Schiavi, Francesca

    AU - Falcioni, Maurizio

    AU - Kwok, Pingling

    AU - Bauters, Catherine

    AU - Lampe, Karen

    AU - Fischer, Markus

    AU - Edelman, Emily

    AU - Benn, Diana E

    AU - Robinson, Bruce G

    AU - Wiegand, Stefanie

    AU - Rasp, Gerd

    AU - Stuck, Boris A

    AU - Hoffmann, Michael M

    AU - Sullivan, Maren

    AU - Sevilla, Maria A

    AU - Weiss, Marjan M

    AU - Peczkowska, Mariola

    AU - Kubaszek, Agata

    AU - Pigny, Pascal

    AU - Ward, Robyn L

    AU - Learoyd, Diana

    AU - Croxson, Michael

    AU - Zabolotny, Dmitry

    AU - Yaremchuk, Svetlana

    AU - Draf, Wolfgang

    AU - Muresan, Mihaela

    AU - Lorenz, Robert R

    AU - Knipping, Stephan

    AU - Strohm, Michael

    AU - Dyckhoff, Gerhard

    AU - Matthias, Christoph

    AU - Reisch, Nicole

    AU - Preuss, Simon F

    AU - Eßer, Dirk

    AU - Walter, Martin A

    AU - Kaftan, Holger

    AU - Stöver, Timo

    AU - Fottner, Christian

    AU - Gorgulla, Harald

    AU - Malekpour, Mahdi

    AU - Zarandy, Masoud Motasaddi

    AU - Schipper, Jörg

    AU - Brase, Christoph

    AU - Glien, Alexander

    AU - Kuhnemund, Matthias

    AU - Koscielny, Sven

    AU - Schwerdtfeger, Peter

    AU - Välimäki, Matti

    AU - Szyfter, Witold

    AU - Finckh, Ulrich

    AU - Zerres, Klaus

    AU - Cascon, Alberto

    AU - Opocher, Giuseppe

    AU - Ridder, Gerd J

    AU - Januszewicz, Andrzej

    AU - Suarez, Carlos

    AU - Eng, Charis

    PY - 2009

    Y1 - 2009

    N2 - "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]"

    AB - "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]"

    U2 - 10.1158/0008-5472.CAN-08-4057

    DO - 10.1158/0008-5472.CAN-08-4057

    M3 - Article

    VL - 69

    SP - 3650

    EP - 3656

    JO - Cancer Research

    JF - Cancer Research

    SN - 0008-5472

    ER -