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

Cheol Ryong Ku, Hyeonseob Lim, Yang Jong Lee, Sun Ho Kim, Daham Kim, Se Hoon Kim, Mi Kyung Lee, Duhee Bang, Eun Jig Lee

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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.

Original languageEnglish
Article number16530
JournalScientific reports
Issue number1
Publication statusPublished - 2021 Dec

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (Grant HI15C1584, HI14C1324 to E.J.L.), Team Science Award funded by Yonsei University College of Medicine (6-2021-0009 to C.R.K), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2021R1I1A1A01058791 to Y.J.L).

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

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