Pierluigi Di Chiaro, Lucia Nacci, Fabiana Arco, Stefania Brandini, Sara Polletti, Andrea Palamidessi, Benedetta Donati, Chiara Soriani, Francesco Gualdrini, Gianmaria Frigè, Luca Mazzarella, Alessia Ciarrocchi, Alessandro Zerbi, Paola Spaggiari, Giorgio Scita, Simona Rodighiero, Iros Barozzi, Giuseppe R Diaferia, Gioacchino Natoli
Intratumor morphological heterogeneity of pancreatic ductal adenocarcinoma (PDAC) predicts clinical outcomes but is only partially understood at the molecular level. To elucidate the gene expression programs underpinning intratumor morphological variation in PDAC, we investigated and deconvoluted at single cell level the molecular profiles of histologically distinct clusters of PDAC cells. We identified three major morphological and functional variants that co-exist in varying proportions in all PDACs, display limited genetic diversity, and are associated with a distinct organization of the extracellular matrix: a glandular variant with classical ductal features; a transitional variant displaying abortive ductal structures and mixed endodermal and myofibroblast-like gene expression; and a poorly differentiated variant lacking ductal features and basement membrane, and showing neuronal lineage priming...
March 18, 2024: Cancer Cell