Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

Abstract We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruite...

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Autores principales:	Cheol Ryong Ku, Hyeonseob Lim, Yang Jong Lee, Sun Ho Kim, Daham Kim, Se Hoon Kim, Mi Kyung Lee, Duhee Bang, Eun Jig Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53ac056270f74c6f9277e1b8a69597e7
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spelling	oai:doaj.org-article:53ac056270f74c6f9277e1b8a69597e72021-12-02T18:51:41ZNovel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant10.1038/s41598-021-95829-32045-2322https://doaj.org/article/53ac056270f74c6f9277e1b8a69597e72021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95829-3https://doaj.org/toc/2045-2322Abstract We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.Cheol Ryong KuHyeonseob LimYang Jong LeeSun Ho KimDaham KimSe Hoon KimMi Kyung LeeDuhee BangEun Jig LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cheol Ryong Ku Hyeonseob Lim Yang Jong Lee Sun Ho Kim Daham Kim Se Hoon Kim Mi Kyung Lee Duhee Bang Eun Jig Lee Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
description	Abstract We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.
format	article
author	Cheol Ryong Ku Hyeonseob Lim Yang Jong Lee Sun Ho Kim Daham Kim Se Hoon Kim Mi Kyung Lee Duhee Bang Eun Jig Lee
author_facet	Cheol Ryong Ku Hyeonseob Lim Yang Jong Lee Sun Ho Kim Daham Kim Se Hoon Kim Mi Kyung Lee Duhee Bang Eun Jig Lee
author_sort	Cheol Ryong Ku
title	Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
title_short	Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
title_full	Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
title_fullStr	Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
title_full_unstemmed	Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant
title_sort	novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without gnas variant
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/53ac056270f74c6f9277e1b8a69597e7
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Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant

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