Abstract LB102: Evaluating the therapeutic and diagnostic utility of clinical whole-genome sequencing in comparison with cancer gene panel testing

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Abstract Targeted cancer gene panel testing has been widely used in cancer genomic medicine; however, clinically relevant non-coding variants and structural variants (SVs) may be missed. To link the variants undetectable by panel testing to cancer diagnosis and treatment, the clinical implementation of whole-genome sequencing is required.To evaluate the clinical utility of genome sequencing, we performed clinical sequencing extended to the genome-wide on 1,050 samples obtained at the Cancer Institute Hospital of JFCR between Oct 2021 and Mar 2024.The cohort consisted of 640 males and 410 females, with a median age of 65 years (15-91), including sarcoma (n = 155), rectal cancer (n = 150), and oral cancer (n = 106). Germline variants in 107 genes associated with hereditary cancer syndromes were identified in 94 cases, and second-hit variants were detected in 34 of these, suggesting driver variants. Among somatic variants, TP53 (n = 610) was most frequently altered, followed by CDKN2A (n = 267), APC (n = 196), and TERT (n = 193).To assess the clinical impact of genome sequencing on therapeutic decision-making, we analyzed 136 cases with recurrent disease. Actionable variants were selected on OncoKB and guidance established by Japanese Society of Medical Oncology, Japan Society of Clinical Oncology, and Japanese Cancer Association. We detected actionable variants in 122 cases. Treatment was proposed in 63 cases, and 12 cases (7.6%) received genome-guided therapy (lung (n = 4), gastric (n = 3), ovarian (n = 2)), comparable to that achieved with panel testing.We compared the analytical performance of genome sequencing with panel tests widely used in Japan: FoundationOne (n = 23), NCC Oncopanel (n = 23), and TruSight Oncology 500 (n = 24). Genome sequencing detected most somatic SNVs and indels identified by these panels, with higher concordance observed when matched normal-tumor DNA samples were used.Genome sequencing detected 48 distinct driver SVs across 86 cases of 16 cancer types, including sarcoma (n = 45), salivary gland cancer (n = 11), and lung cancer (n = 4). Of these, 36 SVs detected in 67 cases were located outside panel target regions and included diagnostically and therapeutically relevant variants.In conclusion, genome sequencing applied to clinical cancer samples enables the detection of variants relevant to diagnosis and treatment, comparable to that of panel testing, while identifying pathogenic SVs beyond panel coverage. Citation Format: Norio Tanaka, Osamu Gotoh, Ippei Fukada, Arisa Ueki, Takayuki Ueno, Shunji Takahashi, Seiichi Mori, Tetuso Noda. Evaluating the therapeutic and diagnostic utility of clinical whole-genome sequencing in comparison with cancer gene panel testing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB102.

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