Endocrine Research Unit, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Ciudad de Mexico 06720, Mexico.
Endocrine Research Unit, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Ciudad de Mexico 06720, Mexico.
Best Pract Res Clin Endocrinol Metab. 2024 May;38(3):101895. doi: 10.1016/j.beem.2024.101895. Epub 2024 Apr 9.
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.
GH 分泌性肿瘤占所有垂体神经内分泌肿瘤（pitNETs）的 15%至 20%，其中 95%发生在散发性环境中，没有可识别的遗传原因。最近的多组学方法已经描述了垂体肿瘤的表观基因组、基因组、转录组、蛋白质组和代谢组学景观。转录组分析使我们能够发现驱动垂体肿瘤分化和基因表达模式的特定转录因子。GH 分泌性、PRL 和 TSH 分泌性 pitNETs 由 POU1F1 驱动；ACTH 分泌性肿瘤由 TBX19 决定；非功能性肿瘤主要来源于性腺分化，由 NR5A1 决定。某些 miRNAs（如 miR-107）的上调与肿瘤进展相关，而其他 miRNAs（如 miR-15a 和 miR-16-1）的下调与肿瘤体积缩小相关。此外，miRNA 表达谱与治疗耐药性和临床结局相关，为潜在的治疗靶点提供了思路。GNAS、PTTG1、GIPR、HGMA2、MAST 中的特定体细胞突变以及与 cAMP、钙信号和 ATP 途径相关的体细胞变异也与肢端肥大症的发生有关。本文重点讨论了散发性肢端肥大症发展的致癌机制，涵盖了一系列复杂的分子改变，最终改变了增殖和凋亡之间的平衡，并导致激素分泌失调。
