In:
Cancer Research and Treatment, Korean Cancer Association, Vol. 56, No. 2 ( 2024-04-15), p. 484-501
Abstract:
Purpose Circulating cell-free DNA (cfDNA) has great potential in clinical oncology. The prognostic and predictive values of cfDNA in non–small cell lung cancer (NSCLC) have been reported, with epidermal growth factor receptor ( 〈 i 〉 EGFR 〈 /i 〉 ), 〈 i 〉 KRAS 〈 /i 〉 , and 〈 i 〉 BRAF 〈 /i 〉 mutations in tumor-derived cfDNAs acting as biomarkers during the early stages of tumor progression and recurrence. However, extremely low tumor-derived DNA rates hinder cfDNA application. We developed an ultra-high-sensitivity lung version 1 (ULV1) panel targeting 〈 i 〉 BRAF 〈 /i 〉 , 〈 i 〉 KRAS 〈 /i 〉 , and 〈 i 〉 EGFR 〈 /i 〉 hotspot mutations using small amounts of cfDNA, allowing for semi-quantitative analysis with excellent limit-of-detection (0.05%).Materials and Methods Mutation analysis was performed on cfDNAs extracted from the plasma of 104 patients with NSCLC by using the ULV1 panel and targeted next-generation sequencing (CT-ULTRA), followed by comparison analysis of mutation patterns previously screened using matched tumor tissue DNA.Results The ULV1 panel demonstrated robust selective amplification of mutant alleles, enabling the detection of mutations with a high degree of analytical sensitivity (limit-of-detection, 0.025%-0.1%) and specificity (87.9%-100%). Applying ULV1 to NSCLC cfDNA revealed 51.1% (23/45) samples with 〈 i 〉 EGFR 〈 /i 〉 mutations, increasing with tumor stage: 8.33% (stage I) to 78.26% (stage IV). Semi-quantitative analysis proved effective for low-mutation-fraction clinical samples. Comparative analysis with PANAMutyper EGFR exhibited substantial concordance (κ=0.84).Conclusion Good detection sensitivity (~80%) was observed despite the limited volume (1 mL) and long-term storage (12-50 months) of plasma used and is expected to increase with high cfDNA inputs. Thus, the ULV1 panel is a fast and cost-effective method for early diagnosis, treatment selection, and clinical follow-up of patients with NSCLC.
Type of Medium:
Online Resource
ISSN:
1598-2998
,
2005-9256
DOI:
10.4143/crt.2023.712
Language:
English
Publisher:
Korean Cancer Association
Publication Date:
2024
detail.hit.zdb_id:
2514151-X
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