Hertz, Daniel L.Kidwell, Kelley M.Thibert, Jacklyn N.Gersch, ChristinaRegan, Meredith M.Skaar, Todd C.Henry, N. LynnHayes, Daniel F.Van Poznak, Catherine H.Rae, James M.2022-10-082022-10-082015-11Hertz DL, Kidwell KM, Thibert JN, et al. Genotyping concordance in DNA extracted from formalin-fixed paraffin embedded (FFPE) breast tumor and whole blood for pharmacogenetic analyses. Mol Oncol. 2015;9(9):1868-1876. doi:10.1016/j.molonc.2015.07.002https://hdl.handle.net/1805/30271Background: Cancer 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. Methods: Cancer 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. Results: Matched 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. Conclusions: No- 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.en-USAttribution 4.0 InternationalCancerFormalin-fixed paraffin embeddedGermline genomePharmacogeneticsSomatic genomeArticle