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Accordingly, we performed multi-omic analyses of <jats:italic>FGFR2<\/jats:italic> genes and FGFR2 signalling molecules in the tissue samples from 36 iCCA na\u00efve patients. Gain-of-function <jats:italic>FGFR2<\/jats:italic> GAs were detected in 7 patients, including missense mutations (n\u2009=\u20093; p.F276C, p.C382R and p.Y375C), translocations (n\u2009=\u20091) and copy number gain (n\u2009=\u20094; CNV\u2009\u2265\u20094). In contrast, among 29 patients with wild-type <jats:italic>FGFR2<\/jats:italic>, 4 cases showed activation of FGFR2 signalling, as they expressed the FGFR2 ligand FGF10 and phosphorylated FGFR2\/FRS2\u03b1 proteins; the remaining 25 cases resulted negative for activated FGFR2 signalling, as they lacked FGFR2 (n\u2009=\u20098) or phosphorylated FRS2\u03b1 (n\u2009=\u200917) expression. Overall, we found that activation of FGFR2 signalling occurs not only in iCCA na\u00efve patients with <jats:italic>FGFR2<\/jats:italic> GAs, but also in a subgroup carrying wild-type <jats:italic>FGFR2<\/jats:italic>. This last finding entails that also this setting of patients could benefit from FGFR targeted therapies, widening indication of these drugs for iCCA patients beyond current approval. Future clinical studies are therefore encouraged to confirm this hypothesis.<\/jats:p>","DOI":"10.1038\/s41598-024-52991-8","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T12:02:32Z","timestamp":1707307352000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Activated FGFR2 signalling as a biomarker for selection of intrahepatic cholangiocarcinoma patients candidate to FGFR targeted therapies"],"prefix":"10.1038","volume":"14","author":[{"given":"Giovanni","family":"Brandi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Relli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzia","family":"Deserti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Palloni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Indio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Astolfi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Serravalle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Mattiaccio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Vasuri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Malvi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Deiana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Abbondanza","family":"Pantaleo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Cescon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Rizzo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaru","family":"Katoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Tavolari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,7]]},"reference":[{"issue":"S1","key":"52991_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/liv.14095","volume":"39","author":"SA Khan","year":"2019","unstructured":"Khan, S. 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