Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

被引：514

作者：

Hedegaard, Jakob ^{[1
]}

Lamy, Philippe ^{[1
]}

Nordentoft, Iver ^{[1
]}

Algaba, Ferran ^{[2
]}

Hoyer, Soren ^{[3
]}

Ulhoi, Benedicte Parm ^{[3
]}

Vang, Soren ^{[1
]}

Reinert, Thomas ^{[1
]}

Hermann, Gregers G. ^{[4
]}

Mogensen, Karin ^{[4
]}

Thomsen, Mathilde Borg Houlberg ^{[1
]}

Nielsen, Morten Muhlig ^{[1
]}

Marquez, Mirari ^{[5
]}

Segersten, Ulrika ^{[6
]}

Aine, Mattias ^{[7
]}

Hoglund, Mattias ^{[7
]}

Birkenkamp-Demtroder, Karin ^{[1
]}

Fristrup, Niels ^{[1
]}

Borre, Michael ^{[8
]}

Hartmann, Arndt ^{[9
]}

Stoehr, Robert ^{[9
]}

Wach, Sven ^{[10
]}

Keck, Bastian ^{[10
]}

Seitz, Anna Katharina ^{[11
]}

Nawroth, Roman ^{[11
]}

Maurer, Tobias ^{[11
]}

Tulic, Cane ^{[12
]}

Simic, Tatjana ^{[13
]}

Junker, Kerstin ^{[14
]}

Horstmann, Marcus ^{[15
]}

Harving, Niels ^{[16
]}

Petersen, Astrid Christine ^{[17
]}

Luz Calle, M. ^{[18
]}

Steyerberg, Ewout W. ^{[19
]}

Beukers, Willemien ^{[20
]}

van Kessel, Kim E. M. ^{[20
]}

Jensen, Jorgen Bjerggaard ^{[8
]}

Pedersen, Jakob Skou ^{[1
]}

Malmstrom, Per-Uno ^{[6
]}

Malats, Nuria ^{[5
]}

Real, Francisco X. ^{[5
,21
]}

Zwarthoff, Ellen C. ^{[20
]}

Orntoft, Torben Falck ^{[1
]}

Dyrskjot, Lars ^{[1
]}

机构：

[1] Aarhus Univ Hosp, Dept Mol Med, DK-8200 Aarhus, Denmark

[2] Univ Autonoma Barcelona, Fundacio Puigvert, Sect Pathol, Barcelona 08025, Spain

[3] Aarhus Univ Hosp, Dept Pathol, DK-8000 Aarhus, Denmark

[4] Frederiksberg Univ Hosp, Dept Urol, DK-2000 Frederiksberg, Denmark

[5] Spanish Natl Canc Res Ctr CNIO, Madrid 28029, Spain

[6] Uppsala Univ, Dept Surg Sci, S-75185 Uppsala, Sweden

[7] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, S-22100 Lund, Sweden

[8] Aarhus Univ Hosp, Dept Urol, DK-8200 Aarhus, Denmark

[9] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, D-91054 Erlangen, Germany

[10] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, D-91054 Erlangen, Germany

[11] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany

[12] Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade 11000, Serbia

[13] Univ Belgrade, Fac Med, Inst Med & Clin Biochem, Belgrade 11000, Serbia

[14] Univ Saarland, Dept Urol, D-66421 Homburg, Germany

[15] Univ Jena, Dept Urol, D-07737 Jena, Germany

[16] Aalborg Univ Hosp, Dept Urol, DK-9000 Aalborg, Denmark

[17] Aalborg Univ Hosp, Dept Pathol, DK-9000 Aalborg, Denmark

[18] Univ Vic, Dept Syst Biol, Barcelona 08500, Spain

[19] Erasmus MC, Dept Publ Hlth, NL-3015 CE Rotterdam, Netherlands

[20] Erasmus MC, Dept Pathol, NL-3015 CE Rotterdam, Netherlands

[21] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona 08003, Spain

来源：

CANCER CELL | 2016年 / 30卷 / 01期

基金：

欧盟第七框架计划;

关键词：

INVASIVE BLADDER-CANCER; LUMINAL SUBTYPES; GENE-EXPRESSION; CELL-CARCINOMA; NOTCH PATHWAY; REVEALS; SIGNATURES; GENOME; BASAL; RNA;

D O I：

10.1016/j.ccell.2016.05.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：27 / 42

页数：16

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