{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T18:19:17Z","timestamp":1772561957759,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Approximately 90% of pancreatic ductal adenocarcinoma (PDAC) cases are driven by the untargetable non\u2010G12C<jats:italic>KRAS<\/jats:italic>mutations, and only a small subset of patients are eligible for FDA\u2010approved precision therapies. The practice of precision therapy in pancreatic cancer was limited by the paucity of targetable genetic alterations, especially in the Asian population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explore therapeutic targets in 499 Chinese PDAC patients, a deep sequencing panel (OncoPanscan\u2122, Genetron health) was used to characterize somatic alterations including point mutations, indels, copy number alterations, gene fusions as well as pathogenic germline variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We performed genomic profiling in 499 Chinese PDAC patients, which revealed somatic driver mutations in<jats:italic>KRAS<\/jats:italic>,<jats:italic>TP53<\/jats:italic>,<jats:italic>CDKN2A<\/jats:italic>,<jats:italic>SMAD4<\/jats:italic>,<jats:italic>ARID1A<\/jats:italic>,<jats:italic>RNF43<\/jats:italic>, and pathogenic germline variants (PGVs) in cancer predisposition genes including<jats:italic>BRCA2<\/jats:italic>,<jats:italic>PALB2<\/jats:italic>, and<jats:italic>ATM<\/jats:italic>. Overall, 20.4% of patients had targetable genomic alterations. About 8.4% of patients carried inactivating germline and somatic variants in<jats:italic>BRCA1\/2<\/jats:italic>and<jats:italic>PALB2<\/jats:italic>, which were susceptible to platinum and PARP inhibitors therapy. Patients with<jats:italic>KRAS<\/jats:italic>wild\u2010type disease and early\u2010onset pancreatic cancer (EOPC) harbored actionable mutations including<jats:italic>BRAF<\/jats:italic>,<jats:italic>EGFR<\/jats:italic>,<jats:italic>ERBB2<\/jats:italic>, and<jats:italic>MAP2K1\/2<\/jats:italic>. Compared to PGV\u2010negative patients, PGV\u2010positive patients were younger and more likely to have a family history of cancer. Furthermore, PGVs in<jats:italic>PALB2<\/jats:italic>,<jats:italic>BRCA2<\/jats:italic>, and<jats:italic>ATM<\/jats:italic>were associated with high PDAC risk in the Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results demonstrated that a genetic screen of actionable genomic variants could facilitate precision therapy and cancer risk reduction in pancreatic cancer patients of Asian ethnicity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5871","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T12:23:33Z","timestamp":1680265413000},"page":"11672-11685","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pathogenic genomic alterations in Chinese pancreatic cancer patients and their therapeutical implications"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhiming","family":"Zhao","sequence":"first","affiliation":[{"name":"Faculty of Hepatopancreatobiliary Surgery The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-0860","authenticated-orcid":false,"given":"Xiaomo","family":"Li","sequence":"additional","affiliation":[{"name":"Hangzhou Jichenjunchuang Medical Laboratory, Co. 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