Characterization of a novel comprehensive genomic profiling test with better detection of heterozygous deletions and RNA-based gene fusion analysis.

Cancer genomic profiling has revolutionized cancer research and clinical practice by facilitating personalized medicine approaches. Next-generation sequencing technologies have played a pivotal role in expanding the possibilities of cancer genomics, providing a comprehensive view of the genomic landscape of tumors and identifying potential therapeutic targets. In Japan, the approval of several cancer-related gene panel tests has accelerated the implementation of cancer genomic medicine. However, there remains a need for evidence-based selection criteria for the different panel tests available. Among these tests, ACTOnco+® stands out as a comprehensive cancer genomic profiling tool. In this study, we compared 110 samples from 29 different tumor types using FoundationOne® CDx (324 genes for DNA analysis) and ACTOnco+® (440 genes for DNA and 31 genes for RNA analysis). Overall, the mutation profiles between the 2 assays exhibited 82.8% positive agreement in reported sequence alterations in clinically actionable genes, including single nucleotide variants and insertions-deletions. Copy number gains showed concordance of 76.9%, and copy number losses in 66.7%. In the case of KIAA1549-BRAF fusion-positive astrocytoma, the fusion event was not detected by DNA only test, but RNA sequencing identified the rearrangement. The patient exhibited clinical benefit from MEK inhibitor treatment. Tumor mutational burden and microsatellite instability (MSI) demonstrated high concordance across various cancer types. ACTOnco+® identified a total of 329 heterozygous deletions, which were subsequently validated for reliability using FISH analysis. Gene profiling with ACTOnco+® exhibited comparable results to FoundationOne® CDx, thereby contributing to future personalized medicine endeavors.