Analytical validation and clinical utilization of K-4CARE™: a comprehensive genomic profiling assay with personalized MRD detection.

Autor:	Nguyen Hoang TP; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen TA; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Tran NHB; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen Hoang VA; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Thi Dao HT; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Tran VU; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen YN; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen AT; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen Thi CT; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Do Thi TT; Medical Genetics Institute, Ho Chi Minh City, Vietnam., Nguyen DS; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Nguyen HN; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Giang H; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam., Tu LN; Medical Genetics Institute, Ho Chi Minh City, Vietnam.; Gene Solutions, Ho Chi Minh City, Vietnam.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular biosciences [Front Mol Biosci] 2024 Feb 09; Vol. 11, pp. 1334808. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024).
DOI:	10.3389/fmolb.2024.1334808
Abstrakt:	Background: Biomarker testing has gradually become standard of care in precision oncology to help physicians select optimal treatment for patients. Compared to single-gene or small gene panel testing, comprehensive genomic profiling (CGP) has emerged as a more time- and tissue-efficient method. This study demonstrated in-depth analytical validation of K-4CARE, a CGP assay that integrates circulating tumor DNA (ctDNA) tracking for residual cancer surveillance. Methods: The assay utilized a panel of 473 cancer-relevant genes with a total length of 1.7 Mb. Reference standards were used to evaluate limit of detection (LOD), concordance, sensitivity, specificity and precision of the assay to detect single nucleotide variants (SNVs), small insertion/deletions (Indels), gene amplification and fusion, microsatellite instability (MSI) and tumor mutational burden (TMB). The assay was then benchmarked against orthogonal methods using 155 clinical samples from 10 cancer types. In selected cancers, top tumor-derived somatic mutations, as ranked by our proprietary algorithm, were used to detect ctDNA in the plasma. Results: For detection of somatic SNVs and Indels, gene fusion and amplification, the assay had sensitivity of >99%, 94% and >99% respectively, and specificity of >99%. Detection of germline variants also achieved sensitivity and specificity of >99%. For TMB measurement, the correlation coefficient between whole-exome sequencing and our targeted panel was 97%. MSI analysis when benchmarked against polymerase chain reaction method showed sensitivity of 94% and specificity of >99%. The concordance between our assay and the TruSight Oncology 500 assay for detection of somatic variants, TMB and MSI measurement was 100%, 89%, and 98% respectively. When CGP-informed mutations were used to personalize ctDNA tracking, the detection rate of ctDNA in liquid biopsy was 79%, and clinical utility in cancer surveillance was demonstrated in 2 case studies. Conclusion: K-4CARE™ assay provides comprehensive and reliable genomic information that fulfills all guideline-based biomarker testing for both targeted therapy and immunotherapy. Integration of ctDNA tracking helps clinicians to further monitor treatment response and ultimately provide well-rounded care to cancer patients. Competing Interests: Authors T-PN, TN, NT, V-AN, AN, HT, V-UT, YN, AN, CN, DN, H-NN, HG, and LT was employed by Gene Solutions. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Nguyen Hoang, Nguyen, Tran, Nguyen Hoang, Thi Dao, Tran, Nguyen, Nguyen, Nguyen Thi, Do Thi, Nguyen, Nguyen, Giang and Tu.)
Databáze:	MEDLINE
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