{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:38:44Z","timestamp":1790624324141,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI25\/00606"],"award-info":[{"award-number":["PI25\/00606"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"award":["PI25\/00606"],"award-info":[{"award-number":["PI25\/00606"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is molecularly characterized by near-universal KRAS mutations and recurrent alterations in TP53, CDKN2A, and SMAD4. Gene fusions are exceptionally rare and have not been established as canonical drivers of PDAC. We report a case of metastatic PDAC harboring an EIF3E::RSPO2 gene fusion in the absence of detectable KRAS or other common driver mutations. A 48-year-old female was diagnosed with stage IV PDAC via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Comprehensive molecular profiling using the Oncomine Precision Assay GX5 revealed no pathogenic single-nucleotide variants, indels, or copy number variations. However, an EIF3E::RSPO2 fusion, predicted to be a gain-of-function alteration, was identified as the sole genomic alteration. Immunohistochemistry showed retained mismatch repair protein expression and preserved SMAD4. Although RSPO2 fusions have been described in preclinical colorectal cancer models and are well-established activators of the Wnt signaling pathway in this setting, their clinical occurrence in PDAC remains poorly documented. This finding indicates a KRAS wild-type tumor with a potential KRAS-independent oncogenic mechanism that may involve aberrant Wnt\/\u03b2-catenin signaling and raises the possibility of a rare, biologically distinct PDAC subset. Comprehensive genomic profiling in advanced PDAC may uncover actionable non-canonical drivers with therapeutic implications.<\/jats:p>","DOI":"10.3390\/ijms27135679","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:57:24Z","timestamp":1782287844000},"page":"5679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EIF3E::RSPO2 Fusion in Metastatic Pancreatic Ductal Adenocarcinoma: A Clinical Case Report Suggesting a Putative KRAS-Independent Molecular Profile"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-3500","authenticated-orcid":false,"given":"Jos\u00e9 Mar\u00eda","family":"Sayagu\u00e9s","sequence":"first","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Abad","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4785-5711","authenticated-orcid":false,"given":"Diego","family":"Bueno-Sacrist\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Sancho","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Belen","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Alonso-M\u00e1rquez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"Moreno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-053X","authenticated-orcid":false,"given":"Juan Carlos","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, 37007 Salamanca, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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