Comparative study on the mutation spectrum of tissue DNA and blood ctDNA in patients with non-small cell lung cancer

Abstract

Background To study the mutations detected in tissue DNA and blood circulating tumor DNA (ctDNA) of patients with advanced lung cancer and analyze the correlations between gene mutations, clinical features, and treatment. Methods Targeted next-generation sequencing (NGS) technology based on probe hybrid capture and Illumina high-throughput sequencing was used to detect the DNA of tumor tissue samples (n=24) and blood samples (n=15) of ctDNA from 28 lung cancer patients with a clear pathological diagnosis. For mutations, the detection range included 4 types of mutations (point mutations, small indels, copy number variations) in all exon regions and partial intron regions of the 556 genes panel. Results The most frequently detected mutant genes in 24 lung cancer tissue samples were TP53 (58.3%, 14/24), EGFR (33.3%, 8/24), LRP1B (25.0%, 6/24), KRAS (20.8%, 5/24), and ARID1A (16.7%, 4/24). The common mutant genes detected in 15 ctDNA samples were TP53 (60%, 5/15), EGFR (33.3%, 5/15), LRP1B (20.0%, 3/15), ERBB4 (3/15), and ARID1A (13.3%, 2/15). Among the 28 patients, 11 patients underwent both tissue DNA and ctDNA detection. The average co-mutation frequency of paired tissue DNA with ctDNA was 38.9% (0–83.3%), and the median value was 37.5%. Conclusions Tissue DNA and ctDNA samples could detect genetic mutations and be consistent. Therefore, ctDNA detection as a method for disease diagnosis and evaluation of tumor molecular status may be helpful for the clinical diagnosis and treatment of lung cancer patients.

The Use of Liquid Biopsy in the Molecular Analysis of Plasma Compared to the Tumour Tissue from a Patient with Brain Metastasis: A Case Report

“…In addition, lung cancers frequently harbour K-RAS mutations, and it is also one of the most common origins of brain metastases [ 22 ], which could potentially explain the present finding in the tumour tissue analysed. Besides, it has been shown that K-RAS alterations found in plasma are significantly predictive of K-RAS tumour status with significant tumour and plasma status consensus [ 26 , 27 ].…”

Guidance for clinicians and patients with non-small cell lung cancer in the time of precision medicine

“…While tissue-based NGS is currently the gold standard, plasma-based NGS is quickly becoming a routine part of clinical practice, and there are currently two FDA-approved plasma-based NGS assays commercially available ( 27 , 28 ). NGS detection of circulating tumor (cell-free) DNA (ctDNA) alterations in plasma is a relatively noninvasive method for screening high-risk populations, guiding early diagnosis and treatment, monitoring relapse, and conducting prognostic evaluation ( 29 ). NILE trial results demonstrate that the real-world impact of ctDNA-based NGS on first-line treatment choice and patient outcomes in aNSCLC begins with a significant reduction in time to treatment initiation versus tissue-based NGS ( 30 ).…”

“…The study confirmed that ctDNA analysis detected actionable mutations at a similar rate as tissue genotyping and similar response rates were achieved regardless of sample sources ( 30 ). However, plasma-based NGS is limited by the low abundance of ctDNA fragments in blood, which affects analytical sensitivity, with up to a 30% false-negative rate ( 4 , 29 ). ctDNA assay results can also be obstructed by clonal hematopoietic and germline alterations ( 4 , 29 ).…”

“…However, plasma-based NGS is limited by the low abundance of ctDNA fragments in blood, which affects analytical sensitivity, with up to a 30% false-negative rate ( 4 , 29 ). ctDNA assay results can also be obstructed by clonal hematopoietic and germline alterations ( 4 , 29 ). Thus, guidelines recommend that ctDNA testing should not be used in lieu of a tissue-based diagnosis ( 4 , 11 , 12 ).…”

“…On the other hand, concurrent plasma- and tissue-based NGS should be used as a complementary approach to detect alterations and tumor burden in real time ( 31 ), thereby enabling monitoring of cancer recurrence and metastasis ( 29 ). In fact, guidelines suggest scheduling the biopsy concurrently with plasma testing referral ( 4 ).…”