Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors

Abstract Neuroendocrine tumors (NETs) of the small intestine undergo large chromosomal and methylation changes. The objective of this study was to identify methylation differences in NETs and consider how the differentially methylated genes may impact patient survival. Genome-wide methylation and ch...

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Autores principales:	Seyoun Byun, Kajsa E. Affolter, Angela K. Snow, Karen Curtin, Austin R. Cannon, Lisa A. Cannon-Albright, Ramya Thota, Deborah W. Neklason
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1b25f39d414403a91699fa476804e6e
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spelling	oai:doaj.org-article:a1b25f39d414403a91699fa476804e6e2021-12-02T14:59:29ZDifferential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors10.1038/s41598-021-91934-52045-2322https://doaj.org/article/a1b25f39d414403a91699fa476804e6e2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91934-5https://doaj.org/toc/2045-2322Abstract Neuroendocrine tumors (NETs) of the small intestine undergo large chromosomal and methylation changes. The objective of this study was to identify methylation differences in NETs and consider how the differentially methylated genes may impact patient survival. Genome-wide methylation and chromosomal copy number variation (CNV) of NETs from the small intestine and appendix were measured. Tumors were divided into three molecular subtypes according to CNV results: chromosome 18 loss (18LOH), Multiple CNV, and No CNV. Comparison of 18LOH tumors with MultiCNV and NoCNV tumors identified 901 differentially methylated genes. Genes from the G-protein coupled receptor (GPCR) pathways are statistically overrepresented in the differentially methylated genes. One of the highlighted genes from the GPCR pathway is somatostatin (SST), a clinical target for NETs. Patient survival based on low versus high methylation in all samples identified four significant genes (p < 0.05) OR2S2, SMILR, RNU6-653P, and AC010543.1. Within the 18LOH molecular subtype tumors, survival differences were identified in high versus low methylation of 24 genes. The most significant is TRHR (p < 0.01), a GPCR with multiple FDA-approved drugs. By separating NETs into different molecular subtypes based on chromosomal changes, we find that multiple GPCRs and their ligands appear to be regulated through methylation and correlated with survival. These results suggest opportunities for better treatment strategies for NETs based on molecular features.Seyoun ByunKajsa E. AffolterAngela K. SnowKaren CurtinAustin R. CannonLisa A. Cannon-AlbrightRamya ThotaDeborah W. NeklasonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Seyoun Byun Kajsa E. Affolter Angela K. Snow Karen Curtin Austin R. Cannon Lisa A. Cannon-Albright Ramya Thota Deborah W. Neklason Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
description	Abstract Neuroendocrine tumors (NETs) of the small intestine undergo large chromosomal and methylation changes. The objective of this study was to identify methylation differences in NETs and consider how the differentially methylated genes may impact patient survival. Genome-wide methylation and chromosomal copy number variation (CNV) of NETs from the small intestine and appendix were measured. Tumors were divided into three molecular subtypes according to CNV results: chromosome 18 loss (18LOH), Multiple CNV, and No CNV. Comparison of 18LOH tumors with MultiCNV and NoCNV tumors identified 901 differentially methylated genes. Genes from the G-protein coupled receptor (GPCR) pathways are statistically overrepresented in the differentially methylated genes. One of the highlighted genes from the GPCR pathway is somatostatin (SST), a clinical target for NETs. Patient survival based on low versus high methylation in all samples identified four significant genes (p < 0.05) OR2S2, SMILR, RNU6-653P, and AC010543.1. Within the 18LOH molecular subtype tumors, survival differences were identified in high versus low methylation of 24 genes. The most significant is TRHR (p < 0.01), a GPCR with multiple FDA-approved drugs. By separating NETs into different molecular subtypes based on chromosomal changes, we find that multiple GPCRs and their ligands appear to be regulated through methylation and correlated with survival. These results suggest opportunities for better treatment strategies for NETs based on molecular features.
format	article
author	Seyoun Byun Kajsa E. Affolter Angela K. Snow Karen Curtin Austin R. Cannon Lisa A. Cannon-Albright Ramya Thota Deborah W. Neklason
author_facet	Seyoun Byun Kajsa E. Affolter Angela K. Snow Karen Curtin Austin R. Cannon Lisa A. Cannon-Albright Ramya Thota Deborah W. Neklason
author_sort	Seyoun Byun
title	Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
title_short	Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
title_full	Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
title_fullStr	Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
title_full_unstemmed	Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
title_sort	differential methylation of g-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a1b25f39d414403a91699fa476804e6e
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Differential methylation of G-protein coupled receptor signaling genes in gastrointestinal neuroendocrine tumors

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