Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.
Aged
Aged, 80 and over
Cyclin D1
/ genetics
Cyclin E
/ genetics
Cystectomy
DNA Copy Number Variations
Female
Humans
Lymph Node Excision
Lymphatic Metastasis
/ genetics
Male
Middle Aged
Multiplex Polymerase Chain Reaction
Oncogene Proteins
/ genetics
Proto-Oncogene Proteins c-myc
/ genetics
Receptor, ErbB-2
/ genetics
Urinary Bladder Neoplasms
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 12 2020
09 12 2020
Historique:
received:
08
04
2020
accepted:
22
09
2020
entrez:
10
12
2020
pubmed:
11
12
2020
medline:
1
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33298978
doi: 10.1038/s41598-020-75869-x
pii: 10.1038/s41598-020-75869-x
pmc: PMC7725833
doi:
Substances chimiques
CCNE1 protein, human
0
Cyclin E
0
MYC protein, human
0
Oncogene Proteins
0
Proto-Oncogene Proteins c-myc
0
Cyclin D1
136601-57-5
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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