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International Journal of Endocrinology
Volume 2015, Article ID 138573, 8 pages
Research Article

Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis

1Department of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK
2Cambridge NIHR Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
3Centre for Rare Diseases and Personalised Medicine, University of Birmingham, Birmingham B15 2TT, UK
4Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UK
5Department of Otology & Skull Base Surgery, Gruppo Otologico, Via Antonio Emmanueli 42, 29121 Piacenza, Italy
6Department of Medical, Oral and Biotechnological Sciences, G. d’Annunzio University, Via dei Vestini 1, 66100 Chieti, Italy
7Department of Urology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa 236-0004, Japan
8Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
9ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain
10Section of Preventive Medicine, Department of Nephrology, Albert Ludwigs University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany
11Department of Clinical Genetics, Birmingham Women’s Hospital, Birmingham B15 2TG, UK

Received 27 June 2014; Revised 23 August 2014; Accepted 26 August 2014

Academic Editor: Claudio Letizia

Copyright © 2015 Andrea Luchetti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


At least 12 genes (FH, HIF2A, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL) have been implicated in inherited predisposition to phaeochromocytoma (PCC), paraganglioma (PGL), or head and neck paraganglioma (HNPGL) and a germline mutation may be detected in more than 30% of cases. Knowledge of somatic mutations contributing to PCC/PGL/HNPGL pathogenesis has received less attention though mutations in HRAS, HIF2A, NF1, RET, and VHL have been reported. To further elucidate the role of somatic mutation in PCC/PGL/HNPGL tumourigenesis, we employed a next generation sequencing strategy to analyse “mutation hotspots” in 50 human cancer genes. Mutations were identified for HRAS (c.37G>C; p.G13R and c.182A>G; p.Q61R) in 7.1% (6/85); for BRAF (c.1799T>A; p.V600E) in 1.2% (1/85) of tumours; and for TP53 (c.1010G>A; p.R337H) in 2.35% (2/85) of cases. Twenty-one tumours harboured mutations in inherited PCC/PGL/HNPGL genes and no HRAS, BRAF, or TP53 mutations occurred in this group. Combining our data with previous reports of HRAS mutations in PCC/PGL we find that the mean frequency of HRAS/BRAF mutations in sporadic PCC/PGL is 8.9% (24/269) and in PCC/PGL with an inherited gene mutation 0% (0/148) suggesting that HRAS/BRAF mutations and inherited PCC/PGL genes mutations might be mutually exclusive. We report the first evidence for BRAF mutations in the pathogenesis of PCC/PGL/HNPGL.