Figure 2.

Phylotranscriptomic tree of pancreatic cancer.

Two initial lineages are evident, largely driven by epigenetic events that separate pancreatic ductal adenocarcinoma into squamous (alternatively named basal-like and quasi-mesenchymal) and classical subtypes.

The classical-pancreatic subtype might contain a spectrum of tumours that resemble pancreatic precursors, paralleling lineages occurring during pancreatic development. We can then discern a classical-progenitor subtype and, although it is unclear as to whether more differentiated progenitor subtypes are due to contamination by normal epithelium, an aberrantly differentiated endocrine exocrine (ADEX) subtype. Although the immunogenic subtype is largely driven by the immune infiltrate of the tumour microenvironment, epithelial-specific mechanisms probably exist that generate such an immune response. Stromal subtypes have also been discerned and, currently, do not appear to be directly associated with epithelial subtypes. The harmonised nomenclature has two broad subtypes: squamous and classical-pancreatic, with the classical-progenitor and ADEX subtypes residing in the latter. The classical-progenitor subtype further subdivides into the immunogenic progenitor and pure classical progenitor subtypes. Adapted from Collisson EA, Bailey P, Chang DK, Biankin AV. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol 2019; 16: 207-220,⁶⁴ with permission from Springer Nature Limited. Copyright © 2019.