Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Jakob Hedegaard; Philippe Lamy; Iver Nordentoft; Ferran Algaba; Søren Høyer; Benedicte Parm Ulhøi; Søren Vang; Thomas Reinert; Gregers G Hermann; Karin Mogensen; Mathilde Borg Houlberg Thomsen; Morten Muhlig Nielsen; Mirari Marquez; Ulrika Segersten; Mattias Aine; Mattias Höglund; Karin Birkenkamp-Demtröder; Niels Fristrup; Michael Borre; Arndt Hartmann; Robert Stöhr; Sven Wach; Bastian Keck; Anna Katharina Seitz; Roman Nawroth; Tobias Maurer; Cane Tulic; Tatjana Simic; Kerstin Junker; Marcus Horstmann; Niels Harving; Astrid Christine Petersen; M Luz Calle; Ewout W Steyerberg; Willemien Beukers; Kim E M van Kessel; Jørgen Bjerggaard Jensen; Jakob Skou Pedersen; Per-Uno Malmström; Núria Malats; Francisco X Real; Ellen C Zwarthoff; Torben Falck Ørntoft; Lars Dyrskjøt

doi:10.1016/j.ccell.2016.05.004

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

Jakob Hedegaard, Philippe Lamy, Iver Nordentoft, Ferran Algaba, Søren Høyer, Benedicte Parm Ulhøi, Søren Vang, Thomas Reinert, Gregers G Hermann, Karin Mogensen, Mathilde Borg Houlberg Thomsen, Morten Muhlig Nielsen, Mirari Marquez, Ulrika Segersten, Mattias Aine, Mattias Höglund, Karin Birkenkamp-Demtröder, Niels Fristrup, Michael Borre, Arndt HartmannRobert Stöhr, Sven Wach, Bastian Keck, Anna Katharina Seitz, Roman Nawroth, Tobias Maurer, Cane Tulic, Tatjana Simic, Kerstin Junker, Marcus Horstmann, Niels Harving, Astrid Christine Petersen, M Luz Calle, Ewout W Steyerberg, Willemien Beukers, Kim E M van Kessel, Jørgen Bjerggaard Jensen, Jakob Skou Pedersen, Per-Uno Malmström, Núria Malats, Francisco X Real, Ellen C Zwarthoff, Torben Falck Ørntoft, Lars Dyrskjøt

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Abstract

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.

Original language	English
Journal	Cancer Cell
Volume	30
Issue	1
Pages (from-to)	27–42
Number of pages	17
ISSN	1535-6108
DOIs	https://doi.org/10.1016/j.ccell.2016.05.004
Publication status	Published - 11 Jul 2016

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Hedegaard, J., Lamy, P., Nordentoft, I., Algaba, F., Høyer, S., Ulhøi, B. P., Vang, S., Reinert, T., Hermann, G. G., Mogensen, K., Thomsen, M. B. H., Nielsen, M. M., Marquez, M., Segersten, U., Aine, M., Höglund, M., Birkenkamp-Demtröder, K., Fristrup, N., Borre, M., ... Dyrskjøt, L. (2016). Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer Cell, 30(1), 27–42. https://doi.org/10.1016/j.ccell.2016.05.004

@article{b1360936eefb451ba197e18cf4b2a396,

title = "Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma",

abstract = "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.",

author = "Jakob Hedegaard and Philippe Lamy and Iver Nordentoft and Ferran Algaba and S{\o}ren H{\o}yer and Ulh{\o}i, {Benedicte Parm} and S{\o}ren Vang and Thomas Reinert and Hermann, {Gregers G} and Karin Mogensen and Thomsen, {Mathilde Borg Houlberg} and Nielsen, {Morten Muhlig} and Mirari Marquez and Ulrika Segersten and Mattias Aine and Mattias H{\"o}glund and Karin Birkenkamp-Demtr{\"o}der and Niels Fristrup and Michael Borre and Arndt Hartmann and Robert St{\"o}hr and Sven Wach and Bastian Keck and Seitz, {Anna Katharina} and Roman Nawroth and Tobias Maurer and Cane Tulic and Tatjana Simic and Kerstin Junker and Marcus Horstmann and Niels Harving and Petersen, {Astrid Christine} and Calle, {M Luz} and Steyerberg, {Ewout W} and Willemien Beukers and {van Kessel}, {Kim E M} and Jensen, {J{\o}rgen Bjerggaard} and Pedersen, {Jakob Skou} and Per-Uno Malmstr{\"o}m and N{\'u}ria Malats and Real, {Francisco X} and Zwarthoff, {Ellen C} and {\O}rntoft, {Torben Falck} and Lars Dyrskj{\o}t",

year = "2016",

month = jul,

day = "11",

doi = "10.1016/j.ccell.2016.05.004",

language = "English",

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journal = "Cancer Cell",

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Hedegaard, J, Lamy, P , Nordentoft, I, Algaba, F, Høyer, S, Ulhøi, BP, Vang, S , Reinert, T, Hermann, GG, Mogensen, K, Thomsen, MBH, Nielsen, MM, Marquez, M, Segersten, U, Aine, M, Höglund, M, Birkenkamp-Demtröder, K, Fristrup, N , Borre, M, Hartmann, A, Stöhr, 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, Malmström, P-U, Malats, N, Real, FX, Zwarthoff, EC, Ørntoft, TF & Dyrskjøt, L 2016, 'Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma', Cancer Cell, vol. 30, no. 1, pp. 27–42. https://doi.org/10.1016/j.ccell.2016.05.004

TY - JOUR

T1 - Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

AU - Hedegaard, Jakob

AU - Lamy, Philippe

AU - Nordentoft, Iver

AU - Algaba, Ferran

AU - Høyer, Søren

AU - Ulhøi, Benedicte Parm

AU - Vang, Søren

AU - Reinert, Thomas

AU - Hermann, Gregers G

AU - Mogensen, Karin

AU - Thomsen, Mathilde Borg Houlberg

AU - Nielsen, Morten Muhlig

AU - Marquez, Mirari

AU - Segersten, Ulrika

AU - Aine, Mattias

AU - Höglund, Mattias

AU - Birkenkamp-Demtröder, Karin

AU - Fristrup, Niels

AU - Borre, Michael

AU - Hartmann, Arndt

AU - Stöhr, Robert

AU - Wach, Sven

AU - Keck, Bastian

AU - Seitz, Anna Katharina

AU - Nawroth, Roman

AU - Maurer, Tobias

AU - Tulic, Cane

AU - Simic, Tatjana

AU - Junker, Kerstin

AU - Horstmann, Marcus

AU - Harving, Niels

AU - Petersen, Astrid Christine

AU - Calle, M Luz

AU - Steyerberg, Ewout W

AU - Beukers, Willemien

AU - van Kessel, Kim E M

AU - Jensen, Jørgen Bjerggaard

AU - Pedersen, Jakob Skou

AU - Malmström, Per-Uno

AU - Malats, Núria

AU - Real, Francisco X

AU - Zwarthoff, Ellen C

AU - Ørntoft, Torben Falck

AU - Dyrskjøt, Lars

PY - 2016/7/11

Y1 - 2016/7/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84979732333&partnerID=8YFLogxK

U2 - 10.1016/j.ccell.2016.05.004

DO - 10.1016/j.ccell.2016.05.004

M3 - Journal article

C2 - 27321955

SN - 1535-6108

VL - 30

SP - 27

EP - 42

JO - Cancer Cell

JF - Cancer Cell

IS - 1

ER -

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

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