Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy

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Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy. / Soave, Armin; Kluwe, Lan; Yu, Hang; Rink, Michael; Gild, Philipp; Vetterlein, Malte W; Marks, Philipp; Sauter, Guido; Fisch, Margit; Meyer, Christian P; Ludwig, Tim; Dahlem, Roland; Minner, Sarah; Pantel, Klaus; Steinbach, Bettina; Schwarzenbach, Heidi.

in: SCI REP-UK, Jahrgang 10, Nr. 1, 09.12.2020, S. 21562.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{e2bd658a55bd4d65ab788b100e625c0b,
title = "Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy",
abstract = "The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.",
author = "Armin Soave and Lan Kluwe and Hang Yu and Michael Rink and Philipp Gild and Vetterlein, {Malte W} and Philipp Marks and Guido Sauter and Margit Fisch and Meyer, {Christian P} and Tim Ludwig and Roland Dahlem and Sarah Minner and Klaus Pantel and Bettina Steinbach and Heidi Schwarzenbach",
year = "2020",
month = dec,
day = "9",
doi = "10.1038/s41598-020-75869-x",
language = "English",
volume = "10",
pages = "21562",
journal = "SCI REP-UK",
issn = "2045-2322",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy

AU - Soave, Armin

AU - Kluwe, Lan

AU - Yu, Hang

AU - Rink, Michael

AU - Gild, Philipp

AU - Vetterlein, Malte W

AU - Marks, Philipp

AU - Sauter, Guido

AU - Fisch, Margit

AU - Meyer, Christian P

AU - Ludwig, Tim

AU - Dahlem, Roland

AU - Minner, Sarah

AU - Pantel, Klaus

AU - Steinbach, Bettina

AU - Schwarzenbach, Heidi

PY - 2020/12/9

Y1 - 2020/12/9

N2 - The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

AB - The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

U2 - 10.1038/s41598-020-75869-x

DO - 10.1038/s41598-020-75869-x

M3 - SCORING: Journal article

C2 - 33298978

VL - 10

SP - 21562

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -