Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 Dec;97(6):763-772.
doi: 10.1111/cen.14827. Epub 2022 Oct 7.

Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients

Federica Guaraldi  1 , Luca Morandi  1   2 , Matteo Zoli  1   2 , Diego Mazzatenta  1   2 , Alberto Righi  3 , Stefania Evangelisti  2 , Francesca Ambrosi  4 , Caterina Tonon  1   2 , Caterina Giannini  2   5 , Ricardo V Lloyd  6 , Sofia Asioli  1   2   7
Affiliations
Observational Study

Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients

Federica Guaraldi et al. Clin Endocrinol (Oxf). 2022 Dec.

Abstract

Objective: To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets.

Design: Retrospective observational study.

Patients and measurements: A total of 64 non-aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1-year follow-up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control.

Results: We found at least one mutation in 17 tumours, including 6/64 non-aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non-aggressive PAs/PITNETs (p < .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non-aggressive ones (p < .05). For X-linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non-aggressive PAs/PITNETs (p < .05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X-linked genes methylation level was lower.

Conclusions: Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA-post-transcriptional regulators and targets of antineoplastic therapies are different in non-aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic-epigenetic analysis, in association with clinico-radiological-pathological data, may be of help in predicting PA/PitNET behaviour.

Keywords: adenoma; methylation profile; pituitary neuroendocrine tumours; prognosis; recurrence; somatic mutation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Circle plot depicting methylation levels of autosomes and X‐linked genes in normal pituitary, aggressive and non‐aggressive PA/PitNETs and carcinomas. PA, pituitary adenoma; PitNET, pituitary neuroendocrine tumour
Figure 2
Figure 2
Methylation plots of autosomes in normal pituitary tissue, non‐aggressive and aggressive PAs/PitNETs. The asterisk (*) indicates CpGs that show statistical differences according to the non‐parametric Kruskal–Wallis test. PA, pituitary adenoma; PitNET, pituitary neuroendocrine tumour
Figure 3
Figure 3
Methylation plots of X‐linked genes in males in normal pituitary tissue, non‐aggressive and aggressive PAs/PitNETs. The asterisk (*) indicates CpGs that show statistical differences according to the non‐parametric Kruskal–Wallis test. PA, pituitary adenoma; PitNET, pituitary neuroendocrine tumour
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Trouillas J, Jaffrain‐Rea M‐L, Vasiljevic A, Raverot G, Roncaroli F, Villa C. How to classify the pituitary neuroendocrine tumors (PitNET)s in 2020. Cancers. 2020;12(2):514. 10.3390/cancers12020514 - DOI - PMC - PubMed
    1. Laws ER, Penn DL, Repetti CS. Advances and controversies in the classification and grading of pituitary tumors. J Endocrinol Invest. 2019;42(2):129‐135. 10.1007/s40618-018-0901-5 - DOI - PubMed
    1. Raverot G, Burman P, McCormack A, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178(1):G1‐G24. 10.1530/EJE-17-0796 - DOI - PubMed
    1. Asa SL, Asioli S, Bozkurt S, et al. Pituitary neuroendocrine tumors (PitNETs): nomenclature evolution, not clinical revolution. Pituitary. 2020;23(3):322‐325. 10.1007/s11102-019-01015-0 - DOI - PubMed
    1. Louis DN, Perry A, Wesseling P, et al. WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021. The 2021;23(8):1231‐1251. 10.1093/neuonc/noab106 - DOI - PMC - PubMed

Publication types