title: Intrinsic basal and luminal subtypes of muscle-invasive bladder cancer.
abstract: Whole-genome analyses have revealed that muscle-invasive bladder cancers (MIBCs) are heterogeneous and can be grouped into basal and luminal subtypes that are highly reminiscent of those found in breast cancer. Basal MIBCs are enriched with squamous and sarcomatoid features and are associated with advanced stage and metastatic disease at presentation. Like basal breast cancers, basal bladder tumours contain a claudin-low subtype that is enriched with biomarkers characteristic of epithelial-to-mesenchymal transition. The stem cell transcription factor ΔNp63α controls basal MIBC gene expression, just as it does in basal breast cancers. Luminal MIBCs are enriched with activating FGFR3 and ERBB3 mutations and ERBB2 amplifications, and their gene expression profiles are controlled by peroxisome proliferator activator receptor γ (PPARγ) and possibly also by oestrogen receptor activation. Luminal bladder cancers can be further subdivided into two subtypes, p53-like and luminal, which can be distinguished from one another by different levels of biomarkers that are characteristic of stromal infiltration, cell cycle progression, and proliferation. Importantly, basal bladder cancers are intrinsically aggressive, but are highly sensitive to cisplatin-based combination chemotherapy. Although the luminal subtypes are not as intrinsically aggressive as basal cancers, p53-like tumours are resistant to chemotherapy and might, therefore, represent a problem for treated patients.
authors: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Woonyoung
authors: W
authors: Choi
authors: Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Bogdan
authors: B
authors: Czerniak
authors: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Andrea
authors: A
authors: Ochoa
authors: Department of Bioinformatics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Xiaoping
authors: X
authors: Su
authors: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Arlene
authors: A
authors: Siefker-Radtke
authors: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Colin
authors: C
authors: Dinney
authors: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: David J
authors: DJ
authors: McConkey
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation; D006801:Humans; D019042:Muscle Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D047495:PPAR gamma / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D047495:PPAR gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D051498:Receptor, Fibroblast Growth Factor, Type 3; D025521:Tumor Suppressor Proteins; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C496365:FGFR3 protein, human