Article ; Online: The molecular biology of sporadic acromegaly.
Best practice & research. Clinical endocrinology & metabolism
2024 Volume 38, Issue 3, Page(s) 101895
Abstract: GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, ... ...
| Abstract | GH-secreting tumors represent 15 % to 20 % of all pituitary neuroendocrine tumors (pitNETs), of which 95 % occur in a sporadic context, without an identifiable inherited cause. Recent multi-omic approaches have characterized the epigenomic, genomic, transcriptomic, proteomic and kynomic landscape of pituitary tumors. Transcriptomic analysis has allowed us to discover specific transcription factors driving the differentiation of pituitary tumors and gene expression patterns. GH-secreting, along with PRL- and TSH-secreting pitNETs are driven by POU1F1; ACTH-secreting tumors are determined by TBX19; and non-functioning tumors, which are predominantly of gonadotrope differentiation are conditioned by NR5A1. Upregulation of certain miRNAs, such as miR-107, is associated with tumor progression, while downregulation of others, like miR-15a and miR-16-1, correlates with tumor size reduction. Additionally, miRNA expression profiles are linked to treatment resistance and clinical outcomes, providing insights into potential therapeutic targets. Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion. |
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| MeSH term(s) | Humans ; Acromegaly/genetics ; Pituitary Neoplasms/genetics ; Pituitary Neoplasms/metabolism ; Pituitary Neoplasms/pathology ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/pathology ; MicroRNAs/genetics | |||||
| Chemical Substances | MicroRNAs | |||||
| Language | English | |||||
| Publishing date | 2024-04-09 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article ; Review | |||||
| ZDB-ID | 2052339-7 | |||||
| ISSN | 1878-1594 ; 1532-1908 ; 1521-690X | |||||
| ISSN (online) | 1878-1594 ; 1532-1908 | |||||
| ISSN | 1521-690X | |||||
| DOI | 10.1016/j.beem.2024.101895 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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