Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime.
Clonal evolution of chemotherapy-resistant urothelial carcinoma / Faltas, Bishoy M; Prandi, Davide; Tagawa, Scott T; Molina, Ana M; Nanus, David M; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A.. - In: NATURE GENETICS. - ISSN 1061-4036. - 48:12(2016), pp. 1490-1499.
Titolo: | Clonal evolution of chemotherapy-resistant urothelial carcinoma | |
Autori: | Faltas, Bishoy M; Prandi, Davide; Tagawa, Scott T; Molina, Ana M; Nanus, David M; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A. | |
Autori Unitn: | ||
Titolo del periodico: | NATURE GENETICS | |
Anno di pubblicazione: | 2016 | |
Numero e parte del fascicolo: | 12 | |
Codice identificativo Scopus: | 2-s2.0-84991628400 | |
Codice identificativo Pubmed: | 27749842 | |
Codice identificativo WOS: | WOS:000389011100009 | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/ng.3692 | |
Handle: | http://hdl.handle.net/11572/161374 | |
Citazione: | Clonal evolution of chemotherapy-resistant urothelial carcinoma / Faltas, Bishoy M; Prandi, Davide; Tagawa, Scott T; Molina, Ana M; Nanus, David M; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A.. - In: NATURE GENETICS. - ISSN 1061-4036. - 48:12(2016), pp. 1490-1499. | |
Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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