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 ra...

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Autores principales:	Armin Soave, Lan Kluwe, Hang Yu, Michael Rink, Philipp Gild, Malte W. Vetterlein, Philipp Marks, Guido Sauter, Margit Fisch, Christian P. Meyer, Tim Ludwig, Roland Dahlem, Sarah Minner, Klaus Pantel, Bettina Steinbach, Heidi Schwarzenbach
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5505756bedc747a0b0d401f3350bbc48
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spelling	oai:doaj.org-article:5505756bedc747a0b0d401f3350bbc482021-12-02T11:43:36ZCopy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy10.1038/s41598-020-75869-x2045-2322https://doaj.org/article/5505756bedc747a0b0d401f3350bbc482020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75869-xhttps://doaj.org/toc/2045-2322Abstract 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.Armin SoaveLan KluweHang YuMichael RinkPhilipp GildMalte W. VetterleinPhilipp MarksGuido SauterMargit FischChristian P. MeyerTim LudwigRoland DahlemSarah MinnerKlaus PantelBettina SteinbachHeidi SchwarzenbachNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Armin Soave Lan Kluwe Hang Yu Michael Rink Philipp Gild Malte W. Vetterlein Philipp Marks Guido Sauter Margit Fisch Christian P. Meyer Tim Ludwig Roland Dahlem Sarah Minner Klaus Pantel Bettina Steinbach Heidi Schwarzenbach Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
description	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.
format	article
author	Armin Soave Lan Kluwe Hang Yu Michael Rink Philipp Gild Malte W. Vetterlein Philipp Marks Guido Sauter Margit Fisch Christian P. Meyer Tim Ludwig Roland Dahlem Sarah Minner Klaus Pantel Bettina Steinbach Heidi Schwarzenbach
author_facet	Armin Soave Lan Kluwe Hang Yu Michael Rink Philipp Gild Malte W. Vetterlein Philipp Marks Guido Sauter Margit Fisch Christian P. Meyer Tim Ludwig Roland Dahlem Sarah Minner Klaus Pantel Bettina Steinbach Heidi Schwarzenbach
author_sort	Armin Soave
title	Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
title_short	Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
title_full	Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
title_fullStr	Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
title_full_unstemmed	Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
title_sort	copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5505756bedc747a0b0d401f3350bbc48
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Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy

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