{"id":64256,"date":"2023-01-26T18:37:05","date_gmt":"2023-01-26T17:37:05","guid":{"rendered":"https:\/\/cri1149.mlcom-dev.net\/?post_type=publications&#038;p=64256"},"modified":"2025-09-11T16:47:58","modified_gmt":"2025-09-11T14:47:58","slug":"molecular-deciphering-of-primary-liver-neuroendocrine-neoplasms-confirms-their-distinct-existence-with-foregut-like-profile","status":"publish","type":"publication","link":"https:\/\/cri1149.mlcom-dev.net\/en\/publication\/molecular-deciphering-of-primary-liver-neuroendocrine-neoplasms-confirms-their-distinct-existence-with-foregut-like-profile\/","title":{"rendered":"Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut-like profile"},"content":{"rendered":"","protected":false},"featured_media":0,"template":"","meta":{"_acf_changed":false},"class_list":["post-64256","publication","type-publication","status-publish","hentry"],"acf":{"numero_de_publication":"J Pathol.","date_de_publication":"20220901","numero_doi":"","equipe":[121],"auteurs-liste":[{"texte_libre":false,"auteur-lien":13215,"auteur-text":""},{"texte_libre":false,"auteur-lien":47152,"auteur-text":""},{"texte_libre":false,"auteur-lien":13204,"auteur-text":""},{"texte_libre":false,"auteur-lien":13146,"auteur-text":""},{"texte_libre":false,"auteur-lien":63209,"auteur-text":""},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Olivia Hentic"},{"texte_libre":true,"auteur-lien":null,"auteur-text":"Fr\u00e9d\u00e9rique Maire"},{"texte_libre":false,"auteur-lien":13148,"auteur-text":""},{"texte_libre":false,"auteur-lien":13102,"auteur-text":""},{"texte_libre":false,"auteur-lien":13152,"auteur-text":""},{"texte_libre":false,"auteur-lien":13135,"auteur-text":""},{"texte_libre":false,"auteur-lien":13150,"auteur-text":""},{"texte_libre":false,"auteur-lien":13054,"auteur-text":""},{"texte_libre":false,"auteur-lien":13055,"auteur-text":""}],"auteurs-manuel":"","liens_externes":null,"liens":[{"lien":"https:\/\/pubmed.ncbi.nlm.nih.gov\/35681273\/"}],"paragraphe":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">Isolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra-hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization. We performed whole-exome sequencing with mutational and copy number analysis. Transcriptomic profiles were compared with pancreatic (n = 31), small-bowel (n = 22), and lung (n = 15) NETs using principal component analysis, unsupervised clustering, and gene set enrichment analysis. Among 27 screened patients, 16 had PHNET (solitary tumor in 63%, median size 11 cm, G2 NETs in 81%) following clinical and pathological review. DNA analyses showed 'foregut-like' genomic profiles with frequent alterations in pathways of Fanconi DNA repair (75%), histone modifiers (58%), adherens junctions (58%), and cell cycle control (50%). The most frequently involved genes were KMT2A (58%), ATM (42%), CDH1, CDKN2C, FANCF, and MEN1 (33% each). Transcriptomic analyses showed that PHNETs clustered closer to foregut (pancreatic, lung) NETs than to midgut (small-bowel) NETs, while remaining a distinct entity with a specific profile. Assessment of potentially predictive biomarkers suggested efficacy of treatments usually active in foregut NETs. In conclusion, PHNETs display a foregut-like molecular profile distinct from other types of NETs, with recurrent molecular alterations. Upon exhaustive work-up to exclude an unrecognized primary tumor, PHNETs should not be considered metastatic NETs from an unknown primary. \u00a9 2022 The Pathological Society of Great Britain and Ireland.<\/p>\r\n<\/div>[:]","paragraphe_en":"[:fr]<h2 class=\"title\" style=\"text-align: justify;\">Abstract<\/h2>\r\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\r\n<p style=\"text-align: justify;\">Isolated hepatic localizations of neuroendocrine tumors (NETs) are generally considered as metastatic NETs of unknown primary but could correspond to primary hepatic NETs (PHNETs), a poorly explored entity. We aimed to describe the clinicopathological and molecular features of PHNETs and compare them with other primary NETs. We assembled a retrospective cohort of patients managed for hepatic localization of NET without extra-hepatic primary tumor after exhaustive clinical, imaging, and immunohistochemical characterization. We performed whole-exome sequencing with mutational and copy number analysis. Transcriptomic profiles were compared with pancreatic (n = 31), small-bowel (n = 22), and lung (n = 15) NETs using principal component analysis, unsupervised clustering, and gene set enrichment analysis. Among 27 screened patients, 16 had PHNET (solitary tumor in 63%, median size 11 cm, G2 NETs in 81%) following clinical and pathological review. DNA analyses showed 'foregut-like' genomic profiles with frequent alterations in pathways of Fanconi DNA repair (75%), histone modifiers (58%), adherens junctions (58%), and cell cycle control (50%). The most frequently involved genes were KMT2A (58%), ATM (42%), CDH1, CDKN2C, FANCF, and MEN1 (33% each). Transcriptomic analyses showed that PHNETs clustered closer to foregut (pancreatic, lung) NETs than to midgut (small-bowel) NETs, while remaining a distinct entity with a specific profile. Assessment of potentially predictive biomarkers suggested efficacy of treatments usually active in foregut NETs. In conclusion, PHNETs display a foregut-like molecular profile distinct from other types of NETs, with recurrent molecular alterations. Upon exhaustive work-up to exclude an unrecognized primary tumor, PHNETs should not be considered metastatic NETs from an unknown primary. \u00a9 2022 The Pathological Society of Great Britain and Ireland.<\/p>\r\n<\/div>[:]","documents":null},"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut-like profile - CRI<\/title>\n<meta name=\"robots\" content=\"noindex, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut-like profile - CRI\" \/>\n<meta property=\"og:url\" content=\"https:\/\/cri1149.mlcom-dev.net\/publication\/molecular-deciphering-of-primary-liver-neuroendocrine-neoplasms-confirms-their-distinct-existence-with-foregut-like-profile\/\" \/>\n<meta property=\"og:site_name\" content=\"CRI\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/CRI-Centre-de-recherche-sur-linflammation-100116118884153\" \/>\n<meta property=\"article:modified_time\" content=\"2025-09-11T14:47:58+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/molecular-deciphering-of-primary-liver-neuroendocrine-neoplasms-confirms-their-distinct-existence-with-foregut-like-profile\/\",\"url\":\"https:\/\/cri1149.mlcom-dev.net\/publication\/molecular-deciphering-of-primary-liver-neuroendocrine-neoplasms-confirms-their-distinct-existence-with-foregut-like-profile\/\",\"name\":\"Molecular deciphering of primary liver neuroendocrine neoplasms confirms their distinct existence with foregut-like profile - 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