Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
Por:
Hedegaard, J, Lamy, P, Nordentoft, I, Algaba, F, Hoyer, S, Ulhoi, BP, Vang, S, Reinert, T, Hermann, GG, Mogensen, K, Thomsen, MBH, Nielsen, MM, Marquez, M, Segersten, U, Aine, M, Hoglund, M, Birkenkamp-Demtroder, K, Fristrup, N, Borre, M, Hartmann, A, Stohr, R, Wach, S, Keck, B, Seitz, AK, Nawroth, R, Maurer, T, Tulic, C, Simic, T, Junker, K, Horstmann, M, Harving, N, Petersen, AC, Calle, ML, Steyerberg, EW, Beukers, W, van Kessel, KEM, Jensen, JB, Pedersen, JS, Malmstrom, PU, Malats, N, Real, FX, Zwarthoff, EC, Orntoft, TF, Dyrskjot, L
Publicada:
11 jul 2016
Resumen:
Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
Filiaciones:
Hedegaard, J:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Lamy, P:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Nordentoft, I:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Algaba, F:
Univ Autonoma Barcelona, Fundacio Puigvert, Sect Pathol, Barcelona 08025, Spain
Hoyer, S:
Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark
Ulhoi, BP:
Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark
Vang, S:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Reinert, T:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Hermann, GG:
Frederiksberg Univ Hosp, Dept Urol, DK-2000 Frederiksberg, Denmark
Mogensen, K:
Frederiksberg Univ Hosp, Dept Urol, DK-2000 Frederiksberg, Denmark
Thomsen, MBH:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Nielsen, MM:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Marquez, M:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Segersten, U:
Uppsala Univ, Dept Surg Sci, S-75185 Uppsala, Sweden
Aine, M:
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, S-22100 Lund, Sweden
Hoglund, M:
Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, S-22100 Lund, Sweden
Birkenkamp-Demtroder, K:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Fristrup, N:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Borre, M:
Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark
Hartmann, A:
Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, D-91054 Erlangen, Germany
Stohr, R:
Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, D-91054 Erlangen, Germany
Wach, S:
Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, D-91054 Erlangen, Germany
Keck, B:
Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, D-91054 Erlangen, Germany
Seitz, AK:
Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany
Nawroth, R:
Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany
Maurer, T:
Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany
Tulic, C:
Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade 11000, Serbia
Simic, T:
Univ Belgrade, Fac Med, Inst Med & Clin Biochem, Belgrade 11000, Serbia
Junker, K:
Univ Saarland, Dept Urol, D-66421 Homburg, Germany
Horstmann, M:
Univ Jena, Dept Urol, D-07737 Jena, Germany
Harving, N:
Aalborg Univ Hosp, Dept Urol, DK-9000 Aalborg, Denmark
Petersen, AC:
Aalborg Univ Hosp, Dept Pathol, DK-9000 Aalborg, Denmark
Calle, ML:
Univ Vic, Dept Syst Biol, Barcelona 08500, Spain
Steyerberg, EW:
Erasmus MC, Dept Publ Hlth, NL-3015 CE Rotterdam, Netherlands
Beukers, W:
Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands
van Kessel, KEM:
Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands
Jensen, JB:
Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark
Pedersen, JS:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Malmstrom, PU:
Uppsala Univ, Dept Surg Sci, S-75185 Uppsala, Sweden
Malats, N:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Real, FX:
Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain
Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain
Zwarthoff, EC:
Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands
Orntoft, TF:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
Dyrskjot, L:
Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark
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