Publications

3D Genomic Mapping Offers New Insight into Pancreatic Precancers

The study investigates pancreatic intraepithelial neoplasias (PanINs), which are precursors to pancreatic cancer, through advanced 3D genomic mapping techniques. Analyzing 46 large samples of normal human pancreas, the researchers employed a machine-learning pipeline for detailed histological reconstruction at single-cell resolution. They discovered an average of 13 PanINs per cm³, suggesting that the normal pancreas may contain hundreds of these precursors, most of which harbor oncogenic KRAS mutations. The findings indicate that most PanINs arise as independent clones with distinct genetic profiles, while some continuous PanINs exhibit multiple KRAS mutations, highlighting their polyclonal origins. This extensive multifocality and genetic heterogeneity raise critical questions about the mechanisms driving precancer initiation and progression, providing a foundation for early detection and intervention strategies for pancreatic cancer.