Quality control materials for pharmacogenomic testing in the clinic

Abstract

Pharmacogenomics has significantly added to our understanding of drug responses in clinical pharmacology, changing the paradigm of treatment decisions. Interrogations of both inherited and somatic variations for therapeutic purposes are increasingly being adopted in clinics, where quality control (QC) materials are required. However, for many pharmacogenomic tests, the acquisition of well-characterized QC materials is often difficult or impossible. In this review, several sources of appropriate QC materials for therapy-associated genetic testing are discussed. Among them, the novel methods for producing renewable controls that resemble patient samples are highlighted. Owing to technological complexity, more efforts are needed to develop proper controls for next-generation sequencing-based assay.

Tumor BRCA testing in ovarian cancer and EQA scheme: our experience of a critical evaluation

“…Consequently, appropriate quantities of high-quality and stable FFPE clinical EQA samples are difficult to obtain [2]. In light of these critical issues, artificial samples, engineered to contain variants of interest, are often used in EQA schemes [4]. Here, we underlined that the DNA sequences flanking the mutations of interest in the artificial fragment must be identical to the in vivo genomic DNA sequences.…”

“…In somatic schemes, genetically engineered samples are generally provided. These artificial controls can be obtained by homogenously mixing mutant versus wild-type (WT) cell lines at defined allelic ratios, which closely mimics the formalinfixed paraffin-embedded (FFPE) tissue block [4].…”

Quality Control of Next-generation Sequencing-based In vitro Diagnostic Test for Onco-relevant Mutations Using Multiplex Reference Materials in Plasma

“…There are several types of commercially available reference materials 7 - 10 . In silico sequences were computationally created which were used for optimization of test performance and to guide the selection of proper bioinformatics tools 11 .…”

Multiplex Cell-Free DNA Reference Materials for Quality Control of Next-Generation Sequencing-Based In Vitro Diagnostic Tests of Colorectal Cancer Tolerance

“…Reference materials (RMs) are control materials with known characteristics (for example, a known genotype) against which test performance can be measured 19 . For clinical NGS assays, the RMs are well-characterized samples that contain known variants at known allele frequencies, and the variations are usually disease associated 20 . RMs can be used for platform validation, experiment validation, informatics pipeline validation, and quality control and proficiency testing 21 .…”