Citations 1
Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia
Douville, Christopher, Parksong, Jeeun , Molin, Marco Dal, Graham, Sarah , Greipp, Patricia T. , Knudson, Ryan A., Curtis, Samuel , Wang, Yuxuan , Dobbyn, Lisa , Popoli, Maria , Ptak, Janine , Silliman, Natalie , Romans, Katharine , Iacobuzio-Donahue, Christine A., Makoohon-Moore, Alvin P., Goggins, Michael, Hruban, Ralph H., Kiemen, Ashley, Bettegowda, Chetan, Kinzler, Kenneth W., Papadopoulos, Nickolas, Wood, Laura D, Vogelstein, B., Goggins, Michael , Hruban, Ralph H. , Papadopoulos, Nickolas , Kinzler, Kenneth W. , Bettegowda, Chetan , Douville, Christopher , Iacobuzio–Donahue, Christine A. , Wang, Yuxuan , Wood, Laura D. , Molin, Marco Dal , Douville, Christopher , Dal Molin, Marco , Knudson, Ryan, Iacobuzio-Donahue, Christine A , Lennon, Anne Marie , Goggins, Michael G , Hruban, Ralph H , Kiemen, Ashley , Bettegowda, Chetan , Kinzler, Kenneth W , Papadopoulos, Nickolas , Wood, Laura D , Vogelstein, Bert , Ptak, Janine , Dobbyn, Lisa , Silliman, Natalie , Greipp, Patricia T , Vogelstein, Bert
Science Advances | February 20, 2026 | Volume: 12 | Issue: 8 | Pages: No page available
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 NCSTN and PSEN2 , genes that code two subunits of the γ-secretase complex. Evaluation of 267 precancerous lesions revealed that extra copies of NCSTN and PSEN2 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 γ-secretase genes are genetically activated oncogenes in the early phases of pancreatic neoplasia.