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Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma
BACKGROUND: Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of ge...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioScientifica
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682230/ https://www.ncbi.nlm.nih.gov/pubmed/23781326 http://dx.doi.org/10.1530/EC-13-0009 |
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author | Crona, Joakim Verdugo, Alberto Delgado Granberg, Dan Welin, Staffan Stålberg, Peter Hellman, Per Björklund, Peyman |
author_facet | Crona, Joakim Verdugo, Alberto Delgado Granberg, Dan Welin, Staffan Stålberg, Peter Hellman, Per Björklund, Peyman |
author_sort | Crona, Joakim |
collection | PubMed |
description | BACKGROUND: Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of genes is constantly growing and the 11 genes together consist of 144 exons. A genetic screening test is extensively time consuming and expensive. Hence, we introduce next-generation sequencing (NGS) as a time-efficient and cost-effective alternative. METHODS: Tumour lesions from three patients with apparently sporadic PCC were subjected to whole exome sequencing utilizing Agilent Sureselect target enrichment system and Illumina Hi seq platform. Bioinformatics analysis was performed in-house using commercially available software. Variants in PCC and PGL susceptibility genes were identified. RESULTS: We have identified 16 unique genetic variants in PCC susceptibility loci in three different PCC, spending less than a 30-min hands-on, in-house time. Two patients had one unique variant each that was classified as probably and possibly pathogenic: NF1 Arg304Ter and RET Tyr791Phe. The RET variant was verified by Sanger sequencing. CONCLUSIONS: NGS can serve as a fast and cost-effective method in the clinical genetic screening of PCC. The bioinformatics analysis may be performed without expert skills. We identified process optimization, characterization of unknown variants and determination of additive effects of multiple variants as key issues to be addressed by future studies. |
format | Online Article Text |
id | pubmed-3682230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioScientifica |
record_format | MEDLINE/PubMed |
spelling | pubmed-36822302013-06-17 Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma Crona, Joakim Verdugo, Alberto Delgado Granberg, Dan Welin, Staffan Stålberg, Peter Hellman, Per Björklund, Peyman Endocr Connect Research BACKGROUND: Recent findings have shown that up to 60% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are caused by germline or somatic mutations in one of the 11 hitherto known susceptibility genes: SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, HIF2A (EPAS1), RET, NF1, TMEM127 and MAX. This list of genes is constantly growing and the 11 genes together consist of 144 exons. A genetic screening test is extensively time consuming and expensive. Hence, we introduce next-generation sequencing (NGS) as a time-efficient and cost-effective alternative. METHODS: Tumour lesions from three patients with apparently sporadic PCC were subjected to whole exome sequencing utilizing Agilent Sureselect target enrichment system and Illumina Hi seq platform. Bioinformatics analysis was performed in-house using commercially available software. Variants in PCC and PGL susceptibility genes were identified. RESULTS: We have identified 16 unique genetic variants in PCC susceptibility loci in three different PCC, spending less than a 30-min hands-on, in-house time. Two patients had one unique variant each that was classified as probably and possibly pathogenic: NF1 Arg304Ter and RET Tyr791Phe. The RET variant was verified by Sanger sequencing. CONCLUSIONS: NGS can serve as a fast and cost-effective method in the clinical genetic screening of PCC. The bioinformatics analysis may be performed without expert skills. We identified process optimization, characterization of unknown variants and determination of additive effects of multiple variants as key issues to be addressed by future studies. BioScientifica 2013-05-28 /pmc/articles/PMC3682230/ /pubmed/23781326 http://dx.doi.org/10.1530/EC-13-0009 Text en © 2013 The Authors http://creativecommons.org/licenses/by/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/deed.en_GB) |
spellingShingle | Research Crona, Joakim Verdugo, Alberto Delgado Granberg, Dan Welin, Staffan Stålberg, Peter Hellman, Per Björklund, Peyman Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title | Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title_full | Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title_fullStr | Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title_full_unstemmed | Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title_short | Next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
title_sort | next-generation sequencing in the clinical genetic screening of patients with pheochromocytoma and paraganglioma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682230/ https://www.ncbi.nlm.nih.gov/pubmed/23781326 http://dx.doi.org/10.1530/EC-13-0009 |
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