The importance of external quality assessments (EQA) and proficiency testing (PT) has come to the forefront of clinical genomics, particularly with the increasing reliance on comprehensive genomic profiling (CGP) for cancer treatment. A recent study from several Japanese laboratories indicates the significant role of these assessments in ensuring accurate detection of genetic variants, which is pivotal for effective cancer therapies.
The study, conducted by the Japan Association for Clinical Laboratory Science (JACLS), involved ten participating laboratories across five university hospitals and five commercial labs. It sought to standardize CGP testing methodologies and assess how well various institutions could identify key cancer-related mutations.
According to the findings, various factors significantly impact the detection of genetic variants, particularly the extraction of nucleic acids from formalin-fixed paraffin-embedded (FFPE) samples. The results emphasized the importance of the variant allele frequency (VAF) for successful mutation detection. For example, testing revealed high detection rates of specific variants at higher VAFs but highlighted the difficulties encountering lower frequencies.
Initially performed on cell line extracts, the first phase of EQA demonstrated a 100% detection rate for KRAS and BRAF mutations when VAF exceeded 10%. Yet, when examining VAF as low as 4.9%, the detection dropped to 67%. Such variation underlines the intricacies of genetic testing and the importance of precision during pre-analytical processes.
More concerning were the discrepancies observed when analyzing DNA extracted from FFPE samples. Despite the best efforts from the ten laboratories, each exhibited diverse capabilities concerning the detection of key variants. Variants with various frequencies observed were often misreported across labs, with significant variability ranging between 13 to 60% relative standard deviation.
The findings call for sharper focus on certain variations, especially concerning BRAF and EGFR genes, which are imperative for targeted cancer therapies. Although high-frequency mutations were detected uniformly, others with lower presence, like BRAF V600K and specific EGFR variants, saw inconsistent reporting.
"This study highlighted the need for enrichment methods to improve detection of clinically significant somatic mutations," said the authors of the article. They pinpointed the importance of refining laboratory pipelines and the extraction processes to curb the observed variations.
Equally important, the study's conclusions highlight the overarching need for standardized procedures. According to the researchers, "variations in NA extraction methods among laboratories, along with updated histopathology protocols could improve DNA specimen quality." These adjustments, alongside regular participation in EQA/PT, could lead to more reliable CGP test results and improved patient care.
The results underlined how external quality assessments play a central role within clinical genomics. They not only promote the accuracy and reliability of individual lab results but also aid laboratories to identify where their process may lack. The standardization of practices through EQA programs could potentially minimize discrepancies caused by methodological differences.
Overall, this comprehensive EQA study asserts the significance of standardized testing methods, particularly the necessity for protocols adjusting to the uniqueness of each laboratory's capabilities. By addressing these issues and continually reviewing testing methods, the quality of cancer genome testing can dramatically improve, paving the way toward more personalized and effective cancer treatments.