Cargando…
Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study
BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detecti...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247705/ https://www.ncbi.nlm.nih.gov/pubmed/25412927 http://dx.doi.org/10.1186/1471-2407-14-854 |
_version_ | 1782346686843060224 |
---|---|
author | Bonberg, Nadine Pesch, Beate Behrens, Thomas Johnen, Georg Taeger, Dirk Gawrych, Katarzyna Schwentner, Christian Wellhäußer, Harald Kluckert, Matthias Leng, Gabriele Nasterlack, Michael Oberlinner, Christoph Stenzl, Arnulf Brüning, Thomas |
author_facet | Bonberg, Nadine Pesch, Beate Behrens, Thomas Johnen, Georg Taeger, Dirk Gawrych, Katarzyna Schwentner, Christian Wellhäußer, Harald Kluckert, Matthias Leng, Gabriele Nasterlack, Michael Oberlinner, Christoph Stenzl, Arnulf Brüning, Thomas |
author_sort | Bonberg, Nadine |
collection | PubMed |
description | BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detection of CNVs in tumor-free men. METHODS: The prospective UroScreen study was designed to investigate the performance of UroVysion™ and other tumor tests for the early detection of bladder cancer in chemical workers from 2003–2010. We analyzed a database compiling CNVs of chromosomes 3, 7, and 17 and at 9p21 that were detected in 191,434 exfoliated urothelial cells from 1,595 men. We assessed the accumulation of CNVs in 1,400 cells isolated from serial samples that were collected from 18 cancer cases up to the time of diagnosis. A generalized estimating equation model was applied to evaluate the influence of age, smoking, and urine status on CNVs in cells from tumor-free men. RESULTS: Tetrasomy of chromosomes 3, 7 and 17, and DNA loss at 9p21 were the most frequently observed forms of CNV. In bladder cancer cases, we observed an accumulation of CNVs that started approximately three years before diagnosis. During the year prior to diagnosis, cells from men with high-grade bladder cancer accumulated more CNVs than those obtained from cases with low-grade cancer (CNV < 2: 7.5% vs. 1.1%, CNV > 2: 16-17% vs. 9-11%). About 1% of cells from tumor-free men showed polysomy of chromosomes 3, 7, or 17 or DNA loss at 9p21. Men aged ≥50 years had 1.3-fold more cells with CNVs than younger men; however, we observed no further age-related accumulation of CNVs in tumor-free men. Significantly more cells with CNVs were detected in samples with low creatinine concentrations. CONCLUSIONS: We found an accumulation of CNVs during the development of bladder cancer starting three years before diagnosis, with more altered cells identified in high-grade tumors. Also, a small fraction of cells with CNVs were exfoliated into urine of tumor-free men, mainly exhibiting tetraploidy or DNA loss at 9p21. Whether these cells are preferentially cleared from the urothelium or are artifacts needs further exploration. |
format | Online Article Text |
id | pubmed-4247705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42477052014-11-30 Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study Bonberg, Nadine Pesch, Beate Behrens, Thomas Johnen, Georg Taeger, Dirk Gawrych, Katarzyna Schwentner, Christian Wellhäußer, Harald Kluckert, Matthias Leng, Gabriele Nasterlack, Michael Oberlinner, Christoph Stenzl, Arnulf Brüning, Thomas BMC Cancer Research Article BACKGROUND: Chromosomal instability in exfoliated urothelial cells has been associated with the development of bladder cancer. Here, we analyzed the accumulation of copy number variations (CNVs) using fluorescence in situ hybridization in cancer cases and explored factors associated with the detection of CNVs in tumor-free men. METHODS: The prospective UroScreen study was designed to investigate the performance of UroVysion™ and other tumor tests for the early detection of bladder cancer in chemical workers from 2003–2010. We analyzed a database compiling CNVs of chromosomes 3, 7, and 17 and at 9p21 that were detected in 191,434 exfoliated urothelial cells from 1,595 men. We assessed the accumulation of CNVs in 1,400 cells isolated from serial samples that were collected from 18 cancer cases up to the time of diagnosis. A generalized estimating equation model was applied to evaluate the influence of age, smoking, and urine status on CNVs in cells from tumor-free men. RESULTS: Tetrasomy of chromosomes 3, 7 and 17, and DNA loss at 9p21 were the most frequently observed forms of CNV. In bladder cancer cases, we observed an accumulation of CNVs that started approximately three years before diagnosis. During the year prior to diagnosis, cells from men with high-grade bladder cancer accumulated more CNVs than those obtained from cases with low-grade cancer (CNV < 2: 7.5% vs. 1.1%, CNV > 2: 16-17% vs. 9-11%). About 1% of cells from tumor-free men showed polysomy of chromosomes 3, 7, or 17 or DNA loss at 9p21. Men aged ≥50 years had 1.3-fold more cells with CNVs than younger men; however, we observed no further age-related accumulation of CNVs in tumor-free men. Significantly more cells with CNVs were detected in samples with low creatinine concentrations. CONCLUSIONS: We found an accumulation of CNVs during the development of bladder cancer starting three years before diagnosis, with more altered cells identified in high-grade tumors. Also, a small fraction of cells with CNVs were exfoliated into urine of tumor-free men, mainly exhibiting tetraploidy or DNA loss at 9p21. Whether these cells are preferentially cleared from the urothelium or are artifacts needs further exploration. BioMed Central 2014-11-20 /pmc/articles/PMC4247705/ /pubmed/25412927 http://dx.doi.org/10.1186/1471-2407-14-854 Text en © Bonberg et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Bonberg, Nadine Pesch, Beate Behrens, Thomas Johnen, Georg Taeger, Dirk Gawrych, Katarzyna Schwentner, Christian Wellhäußer, Harald Kluckert, Matthias Leng, Gabriele Nasterlack, Michael Oberlinner, Christoph Stenzl, Arnulf Brüning, Thomas Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title | Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title_full | Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title_fullStr | Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title_full_unstemmed | Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title_short | Chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
title_sort | chromosomal alterations in exfoliated urothelial cells from bladder cancer cases and healthy men: a prospective screening study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247705/ https://www.ncbi.nlm.nih.gov/pubmed/25412927 http://dx.doi.org/10.1186/1471-2407-14-854 |
work_keys_str_mv | AT bonbergnadine chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT peschbeate chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT behrensthomas chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT johnengeorg chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT taegerdirk chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT gawrychkatarzyna chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT schwentnerchristian chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT wellhaußerharald chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT kluckertmatthias chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT lenggabriele chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT nasterlackmichael chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT oberlinnerchristoph chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT stenzlarnulf chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy AT bruningthomas chromosomalalterationsinexfoliatedurothelialcellsfrombladdercancercasesandhealthymenaprospectivescreeningstudy |