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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 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.

SUBMITTER: Ku CR

PROVIDER: S-EPMC8368009 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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

Ku Cheol Ryong CR Lim Hyeonseob H Lee Yang Jong YJ Kim Sun Ho SH Kim Daham D Kim Se Hoon SH Lee Mi Kyung MK Bang Duhee D Lee Eun Jig EJ

Scientific reports 20210816 1

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. Abse ...[more]

PMID: 34400688

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Project description:Background Tumor consistency recently emerged as a key factor in surgical planning for pituitary adenomas, but its impact on postoperative endocrine function is still unclear. Our study aimed to evaluate the impact of tumor consistency on the development of postoperative pituitary deficiencies. Methods Single-center, retrospective analysis of consecutive pituitary surgeries performed between January 2017 and January 2021 at Policlinico Umberto I in Rome. All patients underwent radiological and biochemical evaluations at baseline, and hormone assessments 3 and 6 months after pituitary surgery. Postoperative MRI studies were used to determine resection rates following surgery. Data on tumor consistency, macroscopic appearance, neurosurgical approach, and intraoperative complications were collected. Results Fifty patients [24 women, mean age 57 ± 13 years, median tumor volume 4800 mm3 [95% CI 620–8828], were included. Greater tumor volume (χ2 = 14.621, p = 0.006) and male sex (χ2 = 12.178, p < 0.001) were associated with worse preoperative endocrine function. All patients underwent transsphenoidal adenomectomy. Fibrous consistency was observed in 10% of patients and was associated with a Ki-67 greater than 3% (χ2 = 8.154, p = 0.04), greater risk of developing postoperative hormone deficiencies (χ2 = 4.485, p = 0.05, OR = 8.571; 95% CI: 0.876–83.908), and lower resection rates (χ2 = 8.148, p = 0.004; OR 1.385, 95% CI; 1.040–1.844). Similarly, worse resection rates were observed in tumors with suprasellar extension (χ2 = 5.048, p = 0.02; OR = 6.000, 95% CI; 1.129–31.880) and CSI (χ2 = 4.000, p = 0.04; OR = 3.857, 95% CI; 0.997–14.916). Conclusions Tumor consistency might provide useful information about postoperative pituitary function, likely due to its impact on surgical procedures. Further prospective studies with larger cohorts are needed to confirm our preliminary findings. Supplementary Information The online version contains supplementary material available at 10.1186/s12902-023-01334-1.

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Dataset Information

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

Publications

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

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