CONTEXT: Hereditary pheochromocytoma/paraganglioma (PC/PGL) accounts for up to 60% of previously considered sporadic tumors. Guidelines suggest that phenotype should guide genetic testing. Next-generation sequencing technology can simultaneously sequence 9 of the 18 known susceptibility genes in a timely, cost-efficient manner. OBJECTIVE: Our aim was to confirm that universal screening is superior to targeted testing in patients with histologically confirmed PC and PGL. METHODS: In two tertiary referral hospitals in Ireland, NGS was carried out on all histologically confirmed cases of PC/PGL diagnosed between 2004 and 2013. The following susceptibility genes were sequenced: VHL, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX. A multiplex ligation-dependent probe amplification analysis was performed in VHL, SDHB, SDHC, SDHD, and SDHAF2 genes to detect deletions and duplications. RESULTS: A total of 31 patients were tested, 31% (n = 10) of whom were found to have a genetic mutation. Of those patients with a positive genotype, phenotype predicted genotype in only 50% (n = 5). Significant genetic mutations that would have been missed in our cohort by phenotypic evaluation alone include a mutation in TMEM127, two mutations in SDHAF2, and two mutations in RET. Target testing would have identified three of the latter mutations based on age criteria. However, 20% of patients (n = 2) would not have satisfied any criteria for targeted testing including one patient with a novel presentation of an SDHAF2 mutation. CONCLUSION: This study supports the value of universal genetic screening for all patients with PC/PGL.
CONTEXT: Hereditary pheochromocytoma/paraganglioma (PC/PGL) accounts for up to 60% of previously considered sporadic tumors. Guidelines suggest that phenotype should guide genetic testing. Next-generation sequencing technology can simultaneously sequence 9 of the 18 known susceptibility genes in a timely, cost-efficient manner. OBJECTIVE: Our aim was to confirm that universal screening is superior to targeted testing in patients with histologically confirmed PC and PGL. METHODS: In two tertiary referral hospitals in Ireland, NGS was carried out on all histologically confirmed cases of PC/PGL diagnosed between 2004 and 2013. The following susceptibility genes were sequenced: VHL, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX. A multiplex ligation-dependent probe amplification analysis was performed in VHL, SDHB, SDHC, SDHD, and SDHAF2 genes to detect deletions and duplications. RESULTS: A total of 31 patients were tested, 31% (n = 10) of whom were found to have a genetic mutation. Of those patients with a positive genotype, phenotype predicted genotype in only 50% (n = 5). Significant genetic mutations that would have been missed in our cohort by phenotypic evaluation alone include a mutation in TMEM127, two mutations in SDHAF2, and two mutations in RET. Target testing would have identified three of the latter mutations based on age criteria. However, 20% of patients (n = 2) would not have satisfied any criteria for targeted testing including one patient with a novel presentation of an SDHAF2 mutation. CONCLUSION: This study supports the value of universal genetic screening for all patients with PC/PGL.
Authors: Tomás P Griffin; Delia Bogdanet; Patrick Navin; Grace Callagy; Paula M O'Shea; Marcia Bell Journal: Ir J Med Sci Date: 2018-02-19 Impact factor: 1.568
Authors: Maria Currás-Freixes; Elena Piñeiro-Yañez; Cristina Montero-Conde; María Apellániz-Ruiz; Bruna Calsina; Veronika Mancikova; Laura Remacha; Susan Richter; Tonino Ercolino; Natalie Rogowski-Lehmann; Timo Deutschbein; María Calatayud; Sonsoles Guadalix; Cristina Álvarez-Escolá; Cristina Lamas; Javier Aller; Julia Sastre-Marcos; Conxi Lázaro; Juan C Galofré; Ana Patiño-García; Amparo Meoro-Avilés; Judith Balmaña-Gelpi; Paz De Miguel-Novoa; Milagros Balbín; Xavier Matías-Guiu; Rocío Letón; Lucía Inglada-Pérez; Rafael Torres-Pérez; Juan M Roldán-Romero; Cristina Rodríguez-Antona; Stephanie M J Fliedner; Giuseppe Opocher; Karel Pacak; Esther Korpershoek; Ronald R de Krijger; Laurent Vroonen; Massimo Mannelli; Martin Fassnacht; Felix Beuschlein; Graeme Eisenhofer; Alberto Cascón; Fátima Al-Shahrour; Mercedes Robledo Journal: J Mol Diagn Date: 2017-05-25 Impact factor: 5.568
Authors: Birke Bausch; Francesca Schiavi; Ying Ni; Jenny Welander; Attila Patocs; Joanne Ngeow; Ulrich Wellner; Angelica Malinoc; Elisa Taschin; Giovanni Barbon; Virginia Lanza; Peter Söderkvist; Adam Stenman; Catharina Larsson; Fredrika Svahn; Jin-Lian Chen; Jessica Marquard; Merav Fraenkel; Martin A Walter; Mariola Peczkowska; Aleksander Prejbisz; Barbara Jarzab; Kornelia Hasse-Lazar; Stephan Petersenn; Lars C Moeller; Almuth Meyer; Nicole Reisch; Arnold Trupka; Christoph Brase; Matthias Galiano; Simon F Preuss; Pingling Kwok; Nikoletta Lendvai; Gani Berisha; Özer Makay; Carsten C Boedeker; Georges Weryha; Karoly Racz; Andrzej Januszewicz; Martin K Walz; Oliver Gimm; Giuseppe Opocher; Charis Eng; Hartmut P H Neumann Journal: JAMA Oncol Date: 2017-09-01 Impact factor: 31.777
Authors: Joakim Crona; Viktor Ljungström; Staffan Welin; Martin K Walz; Per Hellman; Peyman Björklund Journal: PLoS One Date: 2015-07-31 Impact factor: 3.240