{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:33:50Z","timestamp":1787164430879,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T00:00:00Z","timestamp":1543276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["12182"],"award-info":[{"award-number":["12182"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["18178"],"award-info":[{"award-number":["18178"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["Cam\u2010Pac No 602783"],"award-info":[{"award-number":["Cam\u2010Pac No 602783"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Solid pseudopapillary neoplasms (SPN) of the pancreas are rare, low\u2010grade malignant neoplasms that metastasise to the liver or peritoneum in 10\u201315% of cases. They almost invariably present somatic activating mutations of\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    . No comprehensive molecular characterisation of metastatic disease has been conducted to date. We performed whole\u2010exome sequencing and copy\u2010number variation (CNV) analysis of 10 primary SPN and comparative sequencing of five matched primary\/metastatic tumour specimens by high\u2010coverage targeted sequencing of 409 genes. In addition to\n                    <jats:italic>CTNNB1\u2010<\/jats:italic>\n                    activating mutations, we found inactivating mutations of epigenetic regulators (\n                    <jats:italic>KDM6A<\/jats:italic>\n                    ,\n                    <jats:italic>TET1<\/jats:italic>\n                    ,\n                    <jats:italic>BAP1<\/jats:italic>\n                    ) associated with metastatic disease. Most of these alterations were shared between primary and metastatic lesions, suggesting that they occurred before dissemination. Differently from mutations, the majority of CNVs were not shared among lesions from the same patients and affected genes involved in metabolic and pro\u2010proliferative pathways. Immunostaining of 27 SPNs showed that loss or reduction of KDM6A and BAP1 expression was significantly enriched in metastatic SPNs. Consistent with an increased transcriptional response to hypoxia in pancreatic adenocarcinomas bearing\n                    <jats:italic>KDM6A<\/jats:italic>\n                    inactivation, we showed that mutation or reduced KDM6A expression in SPNs is associated with increased expression of the HIF1\u03b1\u2010regulated protein GLUT1 at both primary and metastatic sites. Our results suggest that BAP1 and KDM6A function is a barrier to the development of metastasis in a subset of SPNs, which might open novel avenues for the treatment of this disease. \u00a9 2018 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5180","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T23:05:27Z","timestamp":1539212727000},"page":"123-134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Molecular alterations associated with metastases of solid pseudopapillary neoplasms of the pancreas"],"prefix":"10.1002","volume":"247","author":[{"given":"Eliana","family":"Amato","sequence":"first","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"},{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mafficini","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"},{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Hirabayashi","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"},{"name":"Department of Pathology Tokai University School of Medicine  Isehara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita T","family":"Lawlor","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"},{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Fassan","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Vicentini","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"},{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7807-6935","authenticated-orcid":false,"given":"Stefano","family":"Barbi","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Delfino","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, Section of Pathology University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Sikora","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre University and Hospital Trust of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borislav","family":"Rusev","sequence":"additional","affiliation":[{"name":"ARC\u2010Net Research Centre 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