Dataset Information

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

ABSTRACT: The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer.

SUBMITTER: Huang WL

PROVIDER: S-EPMC4584057 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

Huang Wei-Lun WL Wei Fang F Wong David T DT Lin Chien-Chung CC Su Wu-Chou WC

BioMed research international 20150913

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer t ...[more]

PMID: 26448936

Similar Datasets

Project description:BACKGROUND:Direct comparisons between Guardant360 (G360) circulating tumor DNA (ctDNA) and FoundationOne (F1) tumor biopsy genomic profiling in metastatic colorectal cancer (mCRC) are limited. We aim to assess the concordance across overlapping genes tested in both F1 and G360 in patients with mCRC. MATERIALS AND METHODS:We retrospectively analyzed 75 patients with mCRC who underwent G360 and F1 testing. We evaluated the concordance among gene mutations tested by both G360 and F1 among three categories of patients: untreated, treated without, and treated with EGFR inhibitors, while considering the clonal and/or subclonal nature of each genomic alteration. RESULTS:There was a high rate of concordance in APC, TP53, KRAS, NRAS, and BRAF mutations in the treatment-naive and non-anti-EGFR-treated cohorts. There was increased discordance in the anti-EGFR treated patients in three drivers of anti-EGFR resistance: KRAS, NRAS, and EGFR somatic mutations. Based on percentage of ctDNA, discordant somatic mutations were mostly subclonal instead of clonal and may have limited clinical significance. Most discordant amplifications noted on G360 showed the magnitude below the top decile, occurred in all three cohorts of patients, and were of unknown clinical significance. Serial ctDNA in anti-EGFR treated patients showed the emergence of multiple new alterations that affected the EGFR pathway: EGFR and RAS mutations and MET, RAS, and BRAF amplifications. CONCLUSION:G360 Next-Generation Sequencing platform may be used as an alternative to F1 to detect targetable somatic alterations in non-anti-EGFR treated mCRC, but larger prospective studies are needed to further validate our findings. IMPLICATIONS FOR PRACTICE:Genomic analysis of tissue biopsy is currently the optimal method for identifying DNA genomic alterations to help physicians target specific genes but has many disadvantages that may be mitigated by a circulating free tumor DNA (ctDNA) assay. This study showed a high concordance rate in certain gene mutations in patients who were treatment naive and treated with non-anti-EGFR therapy prior to ctDNA testing. This suggests that ctDNA genomic analysis may potentially be used as an alternative to tumor biopsy to identify appropriate patients for treatment selection in mCRC, but larger prospective studies are needed to further validate concordance among tissue and ctDNA tumor profiling.

Project description:BackgroundThe use of tyrosine kinase inhibitors to target the epidermal growth factor receptor gene (EGFR) in patients with non-small-cell lung cancer is effective but limited by the emergence of drug-resistance mutations. Molecular characterization of circulating tumor cells may provide a strategy for noninvasive serial monitoring of tumor genotypes during treatment.MethodsWe captured highly purified circulating tumor cells from the blood of patients with non-small-cell lung cancer using a microfluidic device containing microposts coated with antibodies against epithelial cells. We performed EGFR mutational analysis on DNA recovered from circulating tumor cells using allele-specific polymerase-chain-reaction amplification and compared the results with those from concurrently isolated free plasma DNA and from the original tumor-biopsy specimens.ResultsWe isolated circulating tumor cells from 27 patients with metastatic non-small-cell lung cancer (median number, 74 cells per milliliter). We identified the expected EGFR activating mutation in circulating tumor cells from 11 of 12 patients (92%) and in matched free plasma DNA from 4 of 12 patients (33%) (P=0.009). We detected the T790M mutation, which confers drug resistance, in circulating tumor cells collected from patients with EGFR mutations who had received tyrosine kinase inhibitors. When T790M was detectable in pretreatment tumor-biopsy specimens, the presence of the mutation correlated with reduced progression-free survival (7.7 months vs. 16.5 months, P<0.001). Serial analysis of circulating tumor cells showed that a reduction in the number of captured cells was associated with a radiographic tumor response; an increase in the number of cells was associated with tumor progression, with the emergence of additional EGFR mutations in some cases.ConclusionsMolecular analysis of circulating tumor cells from the blood of patients with lung cancer offers the possibility of monitoring changes in epithelial tumor genotypes during the course of treatment.

Dataset Information

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

Publications

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets