SEQC2 Oncopanel Sequencing Working Group has just published three manuscripts on targeting small regions of the genome that can aid the detection of rare, but clinically relevant, sub-clonal mutations. Tumor mutational spectra portrayal is critical for exact diagnosis and subsequent fitting of oncotheraphy.
Oncopanel sequencing focuses on some narrow regions of the genome and can distinguish uncommon, yet clinically applicable, sub-clonal mutations. A cross-lab evaluation of pan-cancer comprehensive panels and circulating-tumor DNA liquid-biopsy assays is currently underway with 3 major publications in April this year, two of them co-authored by our Bioinformatics Research Group Leader, dr hab. inż. Paweł Łabaj in Nature Biotechnology and Genome Biology journals.
In the first of the announcements (1) scientists investigated ten different malignant growth cell lines exclusively and their pool, named Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for correctly assessing oncopanel analytical performance. These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.
The second (2) includes a cross-platform multi-lab assessment of eight Pan-Cancer boards to evaluate best practices for oncopanel sequencing and gives significant guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the quick execution, approval, and quality control of oncopanels in clinical use.
Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. In the last announcement (3) the Group reports the discoveries of a multi-site, cross-stage assessment of the analytical performance of five industry-driving ctDNA tests for the best practice rules in precision oncology.
SEQC2 Oncopanel Sequencing Working Group is part of the US FDA led MAQC-IV (also known as SEQC2), the fourth project of MAQC, named Sequencing Quality Control Phase 2 (SEQC2). The essential goal is to create standard analysis protocols and quality control measurements for fit-for-purpose use of NGS data to enhance regulatory science research and precision medicine. Group has participants from academia, government agencies, and industry, including dr hab. inż. Paweł Łabaj. The scope and complexity of this comprehensive study is unprecedented and aims to provide recommendation in support for FDA’s mission in regulatory oversight of NGS diagnostic tests.
1) Jones, W., Gong, B., Novoradovskaya, N. et al. A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency. Genome Biol 22, 111 (2021). https://doi.org/10.1186/s13059-021-02316-z
2) Gong, B., Li, D., Kusko, R. et al. Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions. Genome Biol 22, 109 (2021). https://doi.org/10.1186/s13059-021-02315-0
3) Deveson, I.W., Gong, B., Lai, K. et al. Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology. Nat Biotechnol (2021). https://doi.org/10.1038/s41587-021-00857-z