Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology

Abstract

The Clinical Laboratory Improvement Amendments (CLIA) of 1988 requires that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SOD2, TLR4, and TPMT were validated in a CLIA-accredited laboratory. As no known reference materials were available, DNA samples that were from Coriell Cell Repositories (Camden, NJ) were used for the analytical validation studies. Pharmacogenetic testing methods developed here were shown to be accurate and 100% analytically sensitive and specific. Other CLIA-accredited laboratories interested in offering pharmacogenetic testing for these genetic variants, related to genotype-guided therapy for oncology, could use these publicly available samples as reference materials when developing and validating new genetic tests or refining current assays.

Analytical validation of GenoPharm a clinical genotyping open array panel of 46 pharmacogenes inclusive of variants unique to people of African ancestry

“…This has spurred the development of multiplex genotyping tools to support clinical PGx deployment, starting with the FDA approved AmpliChip from Roche [6]. It has also led to the development and validation of specific PGx testing panels targeting either a disease or population [7][8][9][10].…”