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Adv."],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:p>\n                    We searched for oncogenes activated by copy number increases using whole-genome sequencing data of 535 pancreatic ductal adenocarcinomas (PDACs). We found that gains of 1q were the second most common gain, occurring in 213 (39.8%) of PDACs. Single-cell analysis via fluorescence in situ hybridization on 33 cancers confirmed these results. A portion of 1q, rather than the entire 1q arm, was gained in 75 (14.0%) PDACs, allowing us to pinpoint two ~3-megabase regions of 1q that were nearly always gained. These two regions contained\n                    <jats:italic toggle=\"yes\">NCSTN<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PSEN2<\/jats:italic>\n                    , genes that code two subunits of the \u03b3-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of\n                    <jats:italic toggle=\"yes\">NCSTN<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PSEN2<\/jats:italic>\n                    were common (49%) in noninvasive neoplasms (high-grade pancreatic intraepithelial neoplasms), which are at relatively high risk for progression to PDACs, but uncommon (6%) in low-grade pancreatic intraepithelial neoplasia lesions, which have low malignant potential. We hypothesize that \u03b3-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx7501","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:58:58Z","timestamp":1771613938000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2510-4151","authenticated-orcid":true,"given":"Christopher","family":"Douville","sequence":"first","affiliation":[{"name":"Department of Oncology, the Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA."},{"name":"The Ludwig Center, Johns Hopkins University School of Medicine, 733 N. 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