DAT_CancerMethodsPaper_SNVTumorFoci - samples
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ABSTRACT:
PROVIDER: EGAD00001000035 | EGA |
REPOSITORIES: EGA
Publications
Targeted high throughput sequencing in clinical cancer settings: formaldehyde fixed-paraffin embedded (FFPE) tumor tissues, input amount and tumor heterogeneity.
Kerick Martin M Isau Melanie M Timmermann Bernd B Sültmann Holger H Herwig Ralf R Krobitsch Sylvia S Schaefer Georg G Verdorfer Irmgard I Bartsch Georg G Klocker Helmut H Lehrach Hans H Schweiger Michal R MR
BMC medical genomics 20110929
<h4>Background</h4>Massively parallel sequencing technologies have brought an enormous increase in sequencing throughput. However, these technologies need to be further improved with regard to reproducibility and applicability to clinical samples and settings.<h4>Methods</h4>Using identification of genetic variations in prostate cancer as an example we address three crucial challenges in the field of targeted re-sequencing: Small nucleotide variation (SNV) detection in samples of formalin-fixed ...[more]
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Project description:"Copy number variant detection in multiple foci of three prostate cancer tumors"
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Experimental Design
Fifty-three urines collected after digital rectal exam (post-DRE urine) from rs17632542 genotyped individuals were processed and analyzed by LC-MS in a double-blinded randomized study. The ability to distinguish between homozygous wild-type, heterozygous, or homozygous variant was examined prior to unblinding.
Results
Stable-isotope labeled peptides were used in the detection and quantitation of peptides of interest in each sample. Three peptides were monitored by LC-MS using a PRM method. Analysis of the raw data using Skyline allowed for peak detection and area extraction. Using these data, groupings were predicted using hierarchical clustering in R. Accuracy of the predictions showed 100% concordance across the 53 samples, including individuals homozygous and heterozygous for the SNP.
Conclusions and clinical relevance
The study demonstrates that MS based peptide variant quantitation in urine could be useful in determining patient genotype with high accuracy to complement currently used PSA screening.
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