Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis
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....
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2015-01-01
|
Series: | International Journal of Endocrinology |
Online Access: | http://dx.doi.org/10.1155/2015/138573 |
id |
doaj-47a99b7dfbd645ee944b7cb5c77eaba5 |
---|---|
record_format |
Article |
spelling |
doaj-47a99b7dfbd645ee944b7cb5c77eaba52020-11-24T21:48:20ZengHindawi LimitedInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/138573138573Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing AnalysisAndrea Luchetti0Diana Walsh1Fay Rodger2Graeme Clark3Tom Martin4Richard Irving5Mario Sanna6Masahiro Yao7Mercedes Robledo8Hartmut P. H. Neumann9Emma R. Woodward10Farida Latif11Stephen Abbs12Howard Martin13Eamonn R. Maher14Department of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKCentre for Rare Diseases and Personalised Medicine, University of Birmingham, Birmingham B15 2TT, UKCambridge NIHR Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKDepartment of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKQueen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UKQueen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham B15 2TH, UKDepartment of Otology & Skull Base Surgery, Gruppo Otologico, Via Antonio Emmanueli 42, 29121 Piacenza, ItalyDepartment of Urology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa Ward, Yokohama, Kanagawa 236-0004, JapanHereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, SpainSection of Preventive Medicine, Department of Nephrology, Albert Ludwigs University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, GermanyCentre for Rare Diseases and Personalised Medicine, University of Birmingham, Birmingham B15 2TT, UKCentre for Rare Diseases and Personalised Medicine, University of Birmingham, Birmingham B15 2TT, UKCambridge NIHR Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKCambridge NIHR Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKDepartment of Medical Genetics, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UKAt 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.http://dx.doi.org/10.1155/2015/138573 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Luchetti Diana Walsh Fay Rodger Graeme Clark Tom Martin Richard Irving Mario Sanna Masahiro Yao Mercedes Robledo Hartmut P. H. Neumann Emma R. Woodward Farida Latif Stephen Abbs Howard Martin Eamonn R. Maher |
spellingShingle |
Andrea Luchetti Diana Walsh Fay Rodger Graeme Clark Tom Martin Richard Irving Mario Sanna Masahiro Yao Mercedes Robledo Hartmut P. H. Neumann Emma R. Woodward Farida Latif Stephen Abbs Howard Martin Eamonn R. Maher Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis International Journal of Endocrinology |
author_facet |
Andrea Luchetti Diana Walsh Fay Rodger Graeme Clark Tom Martin Richard Irving Mario Sanna Masahiro Yao Mercedes Robledo Hartmut P. H. Neumann Emma R. Woodward Farida Latif Stephen Abbs Howard Martin Eamonn R. Maher |
author_sort |
Andrea Luchetti |
title |
Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis |
title_short |
Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis |
title_full |
Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis |
title_fullStr |
Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis |
title_full_unstemmed |
Profiling of Somatic Mutations in Phaeochromocytoma and Paraganglioma by Targeted Next Generation Sequencing Analysis |
title_sort |
profiling of somatic mutations in phaeochromocytoma and paraganglioma by targeted next generation sequencing analysis |
publisher |
Hindawi Limited |
series |
International Journal of Endocrinology |
issn |
1687-8337 1687-8345 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/138573 |
work_keys_str_mv |
AT andrealuchetti profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT dianawalsh profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT fayrodger profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT graemeclark profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT tommartin profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT richardirving profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT mariosanna profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT masahiroyao profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT mercedesrobledo profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT hartmutphneumann profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT emmarwoodward profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT faridalatif profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT stephenabbs profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT howardmartin profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis AT eamonnrmaher profilingofsomaticmutationsinphaeochromocytomaandparagangliomabytargetednextgenerationsequencinganalysis |
_version_ |
1725892837196693504 |