Daniel Marrero-Rodríguez (Associate Researcher), Alberto Moscona-Nissan, Jessica Sidauy-Adissi, Fabian Haidenberg-David, Esbeydi Jonguitud-Zumaya, Leonel de Jesus Chávez-Vera, Florencia Martinez-Mendoza, Keiko Taniguchi-Ponciano (Associate Researcher), Moises Mercado (Endocrinologist, Full Professor)
{"title":"散发性肢端肥大症的分子生物学研究","authors":"Daniel Marrero-Rodríguez (Associate Researcher), Alberto Moscona-Nissan, Jessica Sidauy-Adissi, Fabian Haidenberg-David, Esbeydi Jonguitud-Zumaya, Leonel de Jesus Chávez-Vera, Florencia Martinez-Mendoza, Keiko Taniguchi-Ponciano (Associate Researcher), Moises Mercado (Endocrinologist, Full Professor)","doi":"10.1016/j.beem.2024.101895","DOIUrl":null,"url":null,"abstract":"<div><p>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 <em>GNAS</em>, <em>PTTG1</em>, <em>GIPR</em>, <em>HGMA2</em>, <em>MAST</em> 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.</p></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":null,"pages":null},"PeriodicalIF":6.1000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The molecular biology of sporadic acromegaly\",\"authors\":\"Daniel Marrero-Rodríguez (Associate Researcher), Alberto Moscona-Nissan, Jessica Sidauy-Adissi, Fabian Haidenberg-David, Esbeydi Jonguitud-Zumaya, Leonel de Jesus Chávez-Vera, Florencia Martinez-Mendoza, Keiko Taniguchi-Ponciano (Associate Researcher), Moises Mercado (Endocrinologist, Full Professor)\",\"doi\":\"10.1016/j.beem.2024.101895\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>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 <em>GNAS</em>, <em>PTTG1</em>, <em>GIPR</em>, <em>HGMA2</em>, <em>MAST</em> 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.</p></div>\",\"PeriodicalId\":8810,\"journal\":{\"name\":\"Best practice & research. Clinical endocrinology & metabolism\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Best practice & research. 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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.
期刊介绍:
Best Practice & Research Clinical Endocrinology & Metabolism is a serial publication that integrates the latest original research findings into evidence-based review articles. These articles aim to address key clinical issues related to diagnosis, treatment, and patient management.
Each issue adopts a problem-oriented approach, focusing on key questions and clearly outlining what is known while identifying areas for future research. Practical management strategies are described to facilitate application to individual patients. The series targets physicians in practice or training.