TY - JOUR
T1 - Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia
AU - Douville, Christopher
AU - Parksong, Jeeun
AU - Dal Molin, Marco
AU - Graham, Sarah
AU - Greipp, Patricia T.
AU - Knudson, Ryan
AU - Curtis, Samuel
AU - Wang, Yuxuan
AU - Dobbyn, Lisa
AU - Popoli, Maria
AU - Ptak, Janine
AU - Silliman, Natalie
AU - Romans, Katharine
AU - Iacobuzio-Donahue, Christine A.
AU - Makoohon-Moore, Alvin P.
AU - Lennon, Anne Marie
AU - Goggins, Michael
AU - Hruban, Ralph H.
AU - Kiemen, Ashley
AU - Bettegowda, Chetan
AU - Kinzler, Kenneth W.
AU - Papadopoulos, Nickolas
AU - Wood, Laura D.
AU - Vogelstein, Bert
N1 - Publisher Copyright:
© 2026 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
PY - 2026/2/20
Y1 - 2026/2/20
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105030785917
UR - https://www.scopus.com/pages/publications/105030785917#tab=citedBy
U2 - 10.1126/sciadv.adx7501
DO - 10.1126/sciadv.adx7501
M3 - Article
C2 - 41719404
AN - SCOPUS:105030785917
SN - 2375-2548
VL - 12
JO - Science Advances
JF - Science Advances
IS - 8
M1 - eadx7501
ER -