Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.

Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome....

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Autores principales: Angela A G van Tilborg, Lucie C Kompier, Irene Lurkin, Ricardo Poort, Samira El Bouazzaoui, Kirstin van der Keur, Tahlita Zuiverloon, Lars Dyrskjot, Torben F Orntoft, Monique J Roobol, Ellen C Zwarthoff
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/0c4ca61dc0bf4194a0f747c3dda52fcb
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spelling oai:doaj.org-article:0c4ca61dc0bf4194a0f747c3dda52fcb2021-11-18T07:08:01ZSelection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.1932-620310.1371/journal.pone.0043345https://doaj.org/article/0c4ca61dc0bf4194a0f747c3dda52fcb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927958/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.Angela A G van TilborgLucie C KompierIrene LurkinRicardo PoortSamira El BouazzaouiKirstin van der KeurTahlita ZuiverloonLars DyrskjotTorben F OrntoftMonique J RoobolEllen C ZwarthoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43345 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Angela A G van Tilborg
Lucie C Kompier
Irene Lurkin
Ricardo Poort
Samira El Bouazzaoui
Kirstin van der Keur
Tahlita Zuiverloon
Lars Dyrskjot
Torben F Orntoft
Monique J Roobol
Ellen C Zwarthoff
Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
description Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.
format article
author Angela A G van Tilborg
Lucie C Kompier
Irene Lurkin
Ricardo Poort
Samira El Bouazzaoui
Kirstin van der Keur
Tahlita Zuiverloon
Lars Dyrskjot
Torben F Orntoft
Monique J Roobol
Ellen C Zwarthoff
author_facet Angela A G van Tilborg
Lucie C Kompier
Irene Lurkin
Ricardo Poort
Samira El Bouazzaoui
Kirstin van der Keur
Tahlita Zuiverloon
Lars Dyrskjot
Torben F Orntoft
Monique J Roobol
Ellen C Zwarthoff
author_sort Angela A G van Tilborg
title Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
title_short Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
title_full Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
title_fullStr Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
title_full_unstemmed Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
title_sort selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/0c4ca61dc0bf4194a0f747c3dda52fcb
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