Clinical impact of a cancer genomic profiling test using an in-house comprehensive targeted sequencing system

Abstract

Precision medicine is a promising strategy for cancer treatment. In this study, we developed an in-house clinical sequencing system to perform a comprehensive cancer genomic profiling test as a clinical examination and analyzed the utility of this system. Genomic DNA was extracted from tumor tissues and peripheral blood cells collected from 161 patients with different stages and types of cancer. A comprehensive targeted amplicon exome sequencing for 160 cancer-related genes was performed using next-generation sequencing (NGS). The sequencing data were analyzed using an original bioinformatics pipeline, and multiple cancer-specific gene alterations were identified. The success rate of our test was 99% (160/161), while re-biopsy was required for 24% (39/161) of the cases. Potentially actionable and actionable gene alterations were detected in 91% (145/160) and 46% (73/160) of the patients, respectively. The actionable gene alterations were frequently detected in PIK3CA (9%), ERBB2 (8%), and EGFR (4%). High tumor mutation burden (TMB) (≥10 mut/Mb) was observed in 12% (19/160) of the patients. The secondary findings in germline variants considered to be associated with hereditary tumors were detected in 9% (15/160) of the patients. Seventeen patients (11%, 17/160) were treated with genotype-matched therapeutic agents, and the response rate was 47% (8/17). The median turnaround time for physicians was 20 days, and the median survival time after the initial visit was 8.7 months. The results of the present study prove the feasibility of implementing in-house clinical sequencing as a promising laboratory examination technique for precision cancer medicine.

Keywords: actionable gene alteration; clinical sequencing; genomic testing; genotype-matched treatment; precision medicine.

FIGURE 1

Tumor mutation burden (TMB) profile of 160 cancer patients. A, TMB spectrum across tumor types. Violin plots show the distribution of TMB for the top 10 tumor types. Tumor types are arranged from right to left with decreasing median TMB. The width of each plot indicates the frequency of cases with a given TMB. The red line indicates the threshold for cases with TMB‐high status (10 mutations [mut]/Mb). B, Distribution of TMB observed across all patients. NSCLC, non‐small cell lung cancer.