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Nat Cell Biol. 2014 Oct;16(10):982-91, 1-5. doi: 10.1038/ncb3038. Epub 2014 Sep 14.

Bladder cancers arise from distinct urothelial sub-populations.

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Departments of Urology, Genetics &Development, Columbia University, New York, New York 10032, USA.
Department of Pathology, Columbia University, New York, New York 10032, USA.
1] Departments of Urology &Pathology, New York University School of Medicine, New York, New York 10016, USA [2] Veterans Affairs New York Harbour Healthcare System Manhattan Campus, New York, New York 10010, USA.
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.


Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences.

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