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....
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927958/pdf/?tool=EBI |
| _version_ | 1818435243285151744 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:49:47Z |
| format | Article |
| id | doaj.art-0c4ca61dc0bf4194a0f747c3dda52fcb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T16:49:47Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0c4ca61dc0bf4194a0f747c3dda52fcb2022-12-21T22:54:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4334510.1371/journal.pone.0043345Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.Angela A G van TilborgLucie C KompierIrene LurkinRicardo PoortSamira El BouazzaouiKirstin van der KeurTahlita ZuiverloonLars DyrskjotTorben F OrntoftMonique J RoobolEllen C ZwarthoffMicrosatellite 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927958/pdf/?tool=EBI |
| spellingShingle | 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. PLoS ONE |
| title | 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_short | 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22927958/pdf/?tool=EBI |
| work_keys_str_mv | AT angelaagvantilborg selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT lucieckompier selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT irenelurkin selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT ricardopoort selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT samiraelbouazzaoui selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT kirstinvanderkeur selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT tahlitazuiverloon selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT larsdyrskjot selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT torbenforntoft selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT moniquejroobol selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood AT ellenczwarthoff selectionofmicrosatellitemarkersforbladdercancerdiagnosiswithouttheneedforcorrespondingblood |