{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:03:09Z","timestamp":1789041789071,"version":"build-2803163510"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS","award":["PNRR-MR1-2022-12375818"],"award-info":[{"award-number":["PNRR-MR1-2022-12375818"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol Exp"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>von Hippel\u2013Lindau (VHL) disease is a rare hereditary cancer syndrome caused by germline pathogenic variants in the VHL gene. The current standard of care primarily involves surgical resection, which is arbitrarily recommended for renal tumours\u2009\u2265\u20093\u2009cm to reduce the risk of metastasis. However, this approach often leads to repeated surgeries and increased patient morbidity. The key unmet clinical need for VHL patients is the ability to predict the most appropriate therapeutic strategy and the optimal timing for surgical intervention on an individualised basis. Here, we describe a methodology designed to create an integrated map of intra- and inter-tumour heterogeneity in VHL-associated clear cell renal cell carcinoma by combining radiomics, histology, RNA sequencing, whole genome sequencing, and patient-derived organoid cultures from multi-regional tumour biopsies. We hypothesise that decoding this heterogeneity through an integrated analysis of imaging, histopathology, and molecular profiling will enhance diagnostic accuracy and enable more informed and\u00a0personalised therapeutic decisions for VHL patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Relevance statement<\/jats:title>\n                    <jats:p>Due to the current lack of biological or molecular markers assisting clinical decision-making, VHL patients undergo multiple surgical interventions with an incremental risk of complications and morbidity. We expect that our multimodal data study protocol\u00a0will give tools to guide clinical management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Multiregional needle biopsies enable comprehensive analysis even in small ccRCC.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Imaging characteristics suggest the presence of intra- and inter-lesion heterogeneity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tumours are clonally independent and harbour distinct chromosome 3p loss events.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tumours display both intra- and inter-tumour transcriptomics heterogeneity.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Patient-derived organoids grow more easily from areas of low tumour density.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s41747-025-00648-0","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T09:37:25Z","timestamp":1763285845000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intra- and inter-tumoural heterogeneity in von Hippel\u2013Lindau disease-related renal cancer: a multimodal data study protocol"],"prefix":"10.1186","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5398-1776","authenticated-orcid":false,"given":"Isaline","family":"Rowe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Corea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pisu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Genova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ugg\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Ciaparrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Giangrasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni B.","family":"Pipitone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia M.","family":"Scotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Larcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Colciago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco J.","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lucian\u00f2","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Carrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pio","family":"Zeppa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Caputo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Bertini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Montorsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Salonia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Verze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Palmisano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Capitanio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"648_CR1","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1097\/00005792-199711000-00001","volume":"76","author":"ER 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The protocol PNRR-MR1-2022-12375818 received the approval of the Institutional Ethical Committee of IRCCS San Raffaele Hospital (Milan, approval date 14 December 2022), and informed consent was obtained from the patient included in the study. The trial was registered at ClinicalTrials.gov on March 7, 2024. The registration number is NCT06195150.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent was obtained from the patient included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AP is a member of the Scientific Editorial Board of\n                      European Radiology Experimental\n                      (section: cell\/tissue, animal, digital models of human physiopathology) and, as such, did not participate in the selection or review processes of this article. The remaining authors do not have competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"114"}}