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Iver Kristiansen Nordentoft

Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer

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Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer. / Thomsen, Mathilde Borg Houlberg; Nordentoft, Iver; Lamy, Philippe; Vang, Søren; Reinert, Line; Mapendano, Christophe Kamungu; Høyer, Søren; Ørntoft, Torben F; Jensen, Jørgen Bjerggaard; Dyrskjøt, Lars.

In: Scientific Reports, Vol. 7, No. 1, 15.09.2017, p. 11702.

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Author

Thomsen, Mathilde Borg Houlberg ; Nordentoft, Iver ; Lamy, Philippe ; Vang, Søren ; Reinert, Line ; Mapendano, Christophe Kamungu ; Høyer, Søren ; Ørntoft, Torben F ; Jensen, Jørgen Bjerggaard ; Dyrskjøt, Lars. / Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. 11702.

Bibtex

@article{ee76590e6e1448c6a6c720d99313d033,
title = "Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer",
abstract = "Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease. Analysis of adjacent normal urothelium showed low frequency mutations in patients with multifocal disease. Expression profiling showed intra-tumour and intra-patient co-existence of basal- and luminal-like tumour regions, and patients with multifocal disease had a greater degree of genomic and transcriptomic ITH, as well as transformation of adjacent normal cells, compared to patients with unifocal disease. Analysis of the adjacent urothelium may pave the way for therapies targeting the field disease.",
keywords = "Journal Article",
author = "Thomsen, {Mathilde Borg Houlberg} and Iver Nordentoft and Philippe Lamy and S{\o}ren Vang and Line Reinert and Mapendano, {Christophe Kamungu} and S{\o}ren H{\o}yer and {\O}rntoft, {Torben F} and Jensen, {J{\o}rgen Bjerggaard} and Lars Dyrskj{\o}t",
year = "2017",
month = sep,
day = "15",
doi = "10.1038/s41598-017-11291-0",
language = "English",
volume = "7",
pages = "11702",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Comprehensive multiregional analysis of molecular heterogeneity in bladder cancer

AU - Thomsen, Mathilde Borg Houlberg

AU - Nordentoft, Iver

AU - Lamy, Philippe

AU - Vang, Søren

AU - Reinert, Line

AU - Mapendano, Christophe Kamungu

AU - Høyer, Søren

AU - Ørntoft, Torben F

AU - Jensen, Jørgen Bjerggaard

AU - Dyrskjøt, Lars

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease. Analysis of adjacent normal urothelium showed low frequency mutations in patients with multifocal disease. Expression profiling showed intra-tumour and intra-patient co-existence of basal- and luminal-like tumour regions, and patients with multifocal disease had a greater degree of genomic and transcriptomic ITH, as well as transformation of adjacent normal cells, compared to patients with unifocal disease. Analysis of the adjacent urothelium may pave the way for therapies targeting the field disease.

AB - Genetic alterations identified in adjacent normal appearing tissue in bladder cancer patients are indicative of a field disease. Here we assessed normal urothelium transformation and intra-tumour heterogeneity (ITH) in four patients with bladder cancer. Exome sequencing identified private acquired mutations in a lymph node metastasis and local recurrences. Deep re-sequencing revealed presence of at least three and four subclones in two patients with multifocal disease, while no demarcation of subclones was identified in the two patients with unifocal disease. Analysis of adjacent normal urothelium showed low frequency mutations in patients with multifocal disease. Expression profiling showed intra-tumour and intra-patient co-existence of basal- and luminal-like tumour regions, and patients with multifocal disease had a greater degree of genomic and transcriptomic ITH, as well as transformation of adjacent normal cells, compared to patients with unifocal disease. Analysis of the adjacent urothelium may pave the way for therapies targeting the field disease.

KW - Journal Article

U2 - 10.1038/s41598-017-11291-0

DO - 10.1038/s41598-017-11291-0

M3 - Journal article

C2 - 28916750

VL - 7

SP - 11702

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -