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Clonal Evolution of Chemotherapy-Resistant Urothelial Carcinoma
Oleh:
Faltas, Bishoy M.
;
Prandi, Davide
;
Tagawa, Scott T.
;
Molina, Ana M.
;
Nanus, David M.
Jenis:
Article from Journal - ilmiah internasional
Dalam koleksi:
Nature Genetics vol. 48 no. 12 (Dec. 2016)
,
page 1490-1499.
Topik:
Bladder Cancer
;
DNA Sequencing
Ketersediaan
Perpustakaan FK
Nomor Panggil:
N12.K
Non-tandon:
1 (dapat dipinjam: 0)
Tandon:
tidak ada
Lihat Detail Induk
Isi artikel
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.
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