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A Unifying Paradigm for Transcriptional Heterogeneity and Squamous Features in Pancreatic Ductal Adenocarcinoma

Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq defined basal-like subtype. In patients with coexisting basal/squamous and classical/glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical/glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification, and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology, and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.  

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001005519 Illumina HiSeq 2000 Illumina HiSeq 2500 Illumina HiSeq 4000 Illumina NovaSeq 6000 252
Publications Citations
Pancreatic cancers suppress negative feedback of glucose transport to reprogram chromatin for metastasis.
Nat Commun 11: 2020 4055
14
A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma.
Nat Cancer 1: 2020 59-74
95