{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:24:08Z","timestamp":1785284648430,"version":"3.55.0"},"reference-count":55,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precision Oncology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p>It has recently been described that alternative oncogenic drivers may be found in KRAS wild-type ( KRAS<jats:sup>WT<\/jats:sup>) pancreatic cancers. This study aimed to determine the incidence of targetable gene fusions present in KRAS<jats:sup>WT<\/jats:sup>pancreatic adenocarcinoma and response to targeted therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>One hundred consecutive patients with pancreatic adenocarcinoma who underwent targeted next-generation sequencing using DNA sequencing with RNA sequencing (n = 47) or without RNA sequencing (n = 53) at a single institution were included in the study. The frequency and landscape of targetable fusions in KRAS<jats:sup>WT<\/jats:sup>pancreatic adenocarcinoma was characterized and compared with the frequency of fusions in KRAS-mutated ( KRAS<jats:sup>MUT<\/jats:sup>) pancreatic adenocarcinoma. Results were validated in two independent cohorts using data from AACR GENIE (n = 1,252) and TCGA (n = 150). The clinical history of fusion-positive patients who received targeted treatment is described.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Pancreatic cancers from 13 of 100 patients (13%) were found to be KRAS<jats:sup>WT<\/jats:sup>. Targetable fusions were identified in 4\/13 (31%) KRAS<jats:sup>WT<\/jats:sup>tumors compared with 0\/87 (0%) KRAS<jats:sup>MUT<\/jats:sup>pancreatic adenocarcinomas ( P = .0002). One patient with a novel MET fusion had a complete response to targeted therapy with crizotinib that is ongoing at 12+ months of treatment. In the validation cohorts, gene fusions were identified in 18\/97 (19%) and 2\/10 (20%) KRAS<jats:sup>WT<\/jats:sup>tumors reported in the AACR GENIE and TCGA cohorts, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Oncogene fusions are present in KRAS<jats:sup>WT<\/jats:sup>pancreatic adenocarcinomas at an increased frequency when compared with KRAS<jats:sup>MUT<\/jats:sup>pancreatic adenocarcinomas. As these fusions may be susceptible to targeted therapy, molecular analyses for the detection of fusions in KRAS<jats:sup>WT<\/jats:sup>pancreatic adenocarcinomas may warrant increased consideration.<\/jats:p><\/jats:sec>","DOI":"10.1200\/po.20.00265","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T22:08:47Z","timestamp":1610402927000},"page":"65-74","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Identification of Targetable Gene Fusions and Structural Rearrangements to Foster Precision Medicine in<i>KRAS<\/i>Wild-Type Pancreatic Cancer"],"prefix":"10.1200","author":[{"given":"Michael J.","family":"Fusco","sequence":"first","affiliation":[{"name":"Department of Individualized Cancer Management Section of Precision Oncology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daryoush","family":"Saeed-Vafa","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estrella M.","family":"Carballido","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mokenge","family":"Malafa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten L.","family":"Blue","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie K.","family":"Teer","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Walko","sequence":"additional","affiliation":[{"name":"Department of Individualized Cancer Management Section of Precision Oncology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard L.","family":"McLeod","sequence":"additional","affiliation":[{"name":"Geriatric Oncology Consortium, Tampa, FL"},{"name":"USF Taneja College of Pharmacy, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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