Epigenetics and disease progression in neuroendocrine neoplasms.
Epigenetic regulation, including DNA methylation, histone modifications, non-coding RNAs, and higher-order chromatin remodeling, plays a central role in the biology of neuroendocrine neoplasms (NENs). Advances in high-throughput profiling have uncovered epigenetic alterations across pheochromocytoma...
| Publicado en: | Endocrine Reviews Vol. 47; no. 4; pp. 422 - 468 |
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| Autores principales: | , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Oxford University Press / USA
Aug2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195377443&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195377443 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 0163769X 38BM jtl: Endocrine Reviews issn: 0163769X maglogo: N pubinfo: dt: Aug2026 vid: 47 iid: 4 pid: 622 pub: Oxford University Press / USA artinfo: ui: 195377443 10.1210/endrev/bnag005 195377443 ppf: 422 ppct: 46 formats: tig: atl: Epigenetics and disease progression in neuroendocrine neoplasms. aug: au: Lobato, Eduardo C Lafranchi, Andre F Freitas-Castro, Felipe Fagundes, Gustavo F C Sadikovic, Bekim Lines, Kate E Almeida, Madson Q affil: Unidade de Adrenal, Laboratório de Endocrinologia Molecular e Celular LIM25, Divisão de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246-903, Brazil sug: ab: Epigenetic regulation, including DNA methylation, histone modifications, non-coding RNAs, and higher-order chromatin remodeling, plays a central role in the biology of neuroendocrine neoplasms (NENs). Advances in high-throughput profiling have uncovered epigenetic alterations across pheochromocytomas/paragangliomas (PPGLs), gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), lung neuroendocrine neoplasms (LNENs), medullary thyroid carcinoma (MTC), and pituitary NETs (PitNETs). These alterations converge on pathways governing cell cycle control, telomere maintenance, hypoxia signaling, epithelial–mesenchymal transition, and chromatin architecture. Importantly, epigenetic signatures not only mirror genetic backgrounds (eg, SDHx , MEN1 , ATRX , RET) but also provide independent layers of prognostic and predictive information. Distinct methylation profiles, histone modification patterns, and deregulated microRNA/long non-coding RNA networks have been consistently linked to tumor aggressiveness, metastatic potential, and therapeutic resistance. The clinical translation of these insights is rapidly evolving. Methylation-based classifiers and circulating epigenetic markers are emerging as promising tools for early diagnosis, risk stratification, and longitudinal monitoring. Moreover, epigenetic pathways represent attractive therapeutic targets, with DNA methyltransferase inhibitors, histone deacetylase inhibitors, and RNA-modifying enzyme modulators under active investigation. However, significant challenges remain, including methodological heterogeneity, small or retrospective cohorts, and the limited functional validation of candidate biomarkers. Future priorities include prospective multi-institutional validation, integration of epigenomics with other molecular layers in multidimensional classifiers, and the application of spatial and single cell approaches to resolve intra-tumoral heterogeneity. Ultimately, epigenetic research has redefined our understanding of NEN pathogenesis and progression, positioning the epigenome as a promising frontier in precision oncology. Through robust validation, epigenetic biomarkers and therapies may transform the clinical management of NENs. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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