FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.

ABSTRACT: Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance. Phylogenetic analysis confirms that in all cases the urothelial and squamous regions are derived from a common shared precursor. Despite the presence

SUBMITTER: Warrick JI 

PROVIDER: S-EPMC9630410 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature