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. 2020 Jul;146(7):1867-1876.
doi: 10.1007/s00432-020-03192-z. Epub 2020 Mar 27.

Target-based genomic profiling of ctDNA from Chinese non-small cell lung cancer patients: a result of real-world data

Huijuan Chen  1   2 , Aiqin Wang  3 , Jing Wang  3 , Zeming He  3 , Yanqiu Mao  3 , Liming Liu  3
Affiliations

Target-based genomic profiling of ctDNA from Chinese non-small cell lung cancer patients: a result of real-world data

Huijuan Chen et al. J Cancer Res Clin Oncol. 2020 Jul.

Abstract

Purpose: Approximately 30% of NSCLC patients cannot obtain tissue sample or sufficient tissue sample for molecular subtyping. Cell-free circulating tumor DNA (ctDNA) in plasma is a potential alternative specimen type to assess genomic variants in patients with non-small cell lung cancer (NSCLC). The purpose of this study was to identify the genomic alteration profile of ctDNA in real-world Chinese NSCLC patients.

Methods: A total of 325 subjects with pathological diagnosis of NSCLC were enrolled. 10 ml Peripheral blood was collected in streck tube, and ctDNA NGS analysis was carried out using an Ampliseq-based 11-gene panel.

Results: 295 out of 325 patients (90.8%) had detected ctDNA results. In 62.1% (183/295) of these cases, at least one genomic alterations was detected. Frequency altered genes were EGFR (27.8%), TP53 (22.7%), KRAS (21.36%), and PIK3CA (4.75%). EGFR mutation was associated with female, younger age (< 65 years), and adenocarcinoma. The most common mutations in EGFR were L858R (39.4%), exon19 deletions (31.73%), and T790M (18.3%); G13S was the most common alterations in KRAS. TP53 mutation was most occurred in exon7 and exon8. TP53 mutation was significantly more common in patients with history of radiochemotherapy/chemotherapy therapy, and T790M was mainly found in patients with TKIs treatments. Co-existence EGFR mutation with KRAS and different multiple gene co-mutation panels were detected.

Conclusion: In Chinese NSCLC patients, EGFR mutation was significantly associated with female, younger age (< 65 years), and adenocarcinoma. Genomic profiles of NSCLC were associated with the treatment history; TP53 mutation was significantly more frequent in the patients with history of radiochemotherapy/chemotherapy therapy. Various multiple genes co-mutation panels, especially EGFR and KRAS co-mutation, were observed in the ctDNA of Chinese NSCLC patients.

Keywords: Circulating tumor DNA; Next-generation sequencing; Non-small cell lung cancer; Target therapy.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Long tail of genes altered in ctDNA from patients with NSCLC. Frequent alterations given as a percentage of all (N = 295) patients
Fig. 2
Fig. 2
Distribution of EGFR, TP53, and KRAS mutation in NSCLC patients. a Distribution of EGFR mutation that were detected in 83 NSCLC patients (left); detailed mutation types that were not showed in left pie chart (right). b Exons of TP53 mutation that were detected in 67 NSCLC patients (left); top 9 mutation types in TP53 (right). c Distribution of KRAS mutation that were detected in 63 NSCLC patients (left); detailed mutation types that were not showed in left pie chart (right)
Figure 3
Figure 3
Genomic alteration prevalence (%) in circulating tumor DNA (ctDNA) from NSCLC patients with different previous treatments. a Untreated patients. b Progression on radiochemotherapy/chemotherapy. c Progression on EGFR-TKIs EGFRS:EGFR-sensitizing
See this image and copyright information in PMC

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