کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2145604 | 1088800 | 2015 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses](/preview/png/2145604.png)
• Genotyping DNA from FFPE-T specimens is highly concordant (≈99%) with genotyping germline DNA.
• The small loss of genotyping performance is attributable to inadequate DNA yield, not genetic rearrangement.
• Analytic validity of genotyping from FFPE-T on our Sequenom array was documented for 218 cancer pharmacogenetics SNPs.
• FFPE-T DNA is a viable alternative for prospective–retrospective pharmacogenetic analyses of clinical trials.
BackgroundCancer pharmacogenetic studies use archival tumor samples as a DNA source when germline DNA is unavailable. Genotyping DNA from formalin-fixed paraffin embedded tumors (FFPE-T) may be inaccurate due to FFPE storage, genetic aberrations, and/or insufficient DNA extraction. Our objective was to assess the extent and source of genotyping inaccuracy from FFPE-T DNA and demonstrate analytical validity of FFPE-T genotyping of candidate single nucleotide polymorphisms (SNPs) for pharmacogenetic analyses.MethodsCancer pharmacogenetics SNPs were genotyped by Sequenom MassARRAYs in DNA harvested from matched FFPE-T, FFPE lymph node (FFPE-LN), and whole blood leukocyte samples obtained from breast cancer patients. No- and discordant-call rates were calculated for each tissue type and SNP. Analytical validity was defined as any SNP with <5% discordance between FFPE-T and blood and <10% discordance plus no-calls.ResultsMatched samples from 114 patients were genotyped for 247 SNPs. No-call rate in FFPE-T was greater than FFPE-LN and blood (4.3% vs. 3.0% vs. 0.5%, p < 0.001). Discordant-call rate between FFPE-T and blood was very low, but greater than that between FFPE-LN and blood (1.1% vs. 0.3%, p < 0.001). Samples with heterozygous genotypes were more likely to be no- or discordantly-called in either tissue (p < 0.001). Analytical validity of FFPE-T genotyping was demonstrated for 218 (88%) SNPs.ConclusionsNo- and discordant-call rates were below concerning thresholds, confirming that most SNPs can be accurately genotyped from FFPE-T on our Sequenom platform. FFPE-T is a viable DNA source for prospective–retrospective pharmacogenetic analyses of clinical trial cohorts.
Journal: Molecular Oncology - Volume 9, Issue 9, November 2015, Pages 1868–1876