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Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations

INTRODUCTION: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX...

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Autores principales: Chen, Jingci, Wu, Yan, Wang, Pengyan, Wu, Huanwen, Tong, Anli, Chang, Xiaoyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428080/
https://www.ncbi.nlm.nih.gov/pubmed/34261040
http://dx.doi.org/10.1530/EC-21-0300
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author Chen, Jingci
Wu, Yan
Wang, Pengyan
Wu, Huanwen
Tong, Anli
Chang, Xiaoyan
author_facet Chen, Jingci
Wu, Yan
Wang, Pengyan
Wu, Huanwen
Tong, Anli
Chang, Xiaoyan
author_sort Chen, Jingci
collection PubMed
description INTRODUCTION: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP. METHODS: Eighteen CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in two cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in fifteen cases (including the two cases with TRS performed), with three cases excluded due to the limited amount of tissue. RESULTS: Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtaposed with the PCC/PGL components, with a highly variable percentage (10–80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL. CONCLUSIONS: We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets.
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spelling pubmed-84280802021-09-13 Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations Chen, Jingci Wu, Yan Wang, Pengyan Wu, Huanwen Tong, Anli Chang, Xiaoyan Endocr Connect Research INTRODUCTION: Composite pheochromocytoma/paraganglioma (CP) is a rare neoplasm with most cases presented as single reports. Little is known about its pathogenesis and relationship with ordinary pheochromocytoma (PCC) or paraganglioma (PGL). Our study is aimed at analyzing the status of SDH and ATRX and identifying novel genetic changes in CP. METHODS: Eighteen CP cases were collected. SDH and ATRX status was screened by immunohistochemistry. Targeted region sequencing (TRS) was successfully performed on formalin-fixed paraffin-embedded tissues in two cases within 3 years. Based on the TRS result, Sanger sequencing of BRAF and HRAS was performed in fifteen cases (including the two cases with TRS performed), with three cases excluded due to the limited amount of tissue. RESULTS: Histopathologically, all the cases were composite PCC/PGL-ganglioneuroma (GN). The GN components were either closely admixed or juxtaposed with the PCC/PGL components, with a highly variable percentage (10–80%). All cases stained positive for SDHB and ATRX. HRAS and BRAF mutations were identified during TRS. In the subsequent Sanger sequencing, 20.0% (3/15) harbored BRAF mutations (K601E and K601N) and 46.7% (7/15) harbored HRAS mutations (Q61R, Q61L, G13R). The mutation rates were both significantly higher than reported in ordinary PCC/PGL. CONCLUSIONS: We demonstrated that composite PCC/PGL-GN might be a unique entity with frequent HRAS and BRAF mutations rather than genetic changes of SDH and ATRX. Our findings revealed the possible pathogenesis of composite PCC/PGL-GN and provided clues for potential treatment targets. Bioscientifica Ltd 2021-07-14 /pmc/articles/PMC8428080/ /pubmed/34261040 http://dx.doi.org/10.1530/EC-21-0300 Text en © The authors https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Research
Chen, Jingci
Wu, Yan
Wang, Pengyan
Wu, Huanwen
Tong, Anli
Chang, Xiaoyan
Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title_full Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title_fullStr Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title_full_unstemmed Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title_short Composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of SDH and ATRX status, and identification of frequent HRAS and BRAF mutations
title_sort composite pheochromocytoma/paraganglioma-ganglioneuroma: analysis of sdh and atrx status, and identification of frequent hras and braf mutations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428080/
https://www.ncbi.nlm.nih.gov/pubmed/34261040
http://dx.doi.org/10.1530/EC-21-0300
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