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Detection of Loss of Heterozygosity in cfDNA of Advanced EGFR- or KRAS-Mutated Non-Small-Cell Lung Cancer Patients
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 1
- Publication Year :
- 2019
- Publisher :
- MDPI, 2019.
-
Abstract
- Liquid biopsy is currently approved for management of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients. However, one unanswered question is whether the rate of cell-free DNA (cfDNA)-negative samples is due to technical limitations rather than to tumor genetic characteristics. Using four microsatellite markers that map specific chromosomal loci often lost in lung cancer, we conducted a pilot study to investigate whether other alterations, such as loss of heterozygosity (LOH), could be detected in EGFR-negative cfDNA. We analyzed EGFR-mutated NSCLC patients (n = 24) who were positive or negative for EGFR mutations in cfDNA and compared the results with a second cohort of 24 patients bearing KRAS-mutated cancer, which served as a representative control population not exposed to targeted therapy. The results showed that in EGFR-negative post-tyrosine-kinase-inhibitor (TKI) cfDNAs, LOH frequency was significantly higher than in both pre- and post-TKI EGFR-positive cfDNAs. By contrast, no association between KRAS status in cfDNA and number of LOH events was found. In conclusion, our study indicates the feasibility of detecting LOH events in cfDNA from advanced NSCLC and suggests LOH analysis as a new candidate molecular assay to integrate mutation-specific assays.
- Subjects :
- 0301 basic medicine
Oncology
Male
Lung Neoplasms
medicine.medical_treatment
non-small cell lung cancer (NSCLC)
Loss of Heterozygosity
Pilot Projects
medicine.disease_cause
Targeted therapy
Loss of heterozygosity
0302 clinical medicine
Carcinoma, Non-Small-Cell Lung
80 and over
Epidermal growth factor receptor
Non-Small-Cell Lung
Spectroscopy
Aged, 80 and over
biology
Cell-free DNA (cfDNA)
Epidermal growth factor receptor (EGFR)
Kirsten rat sarcoma homologous (KRAS)
Liquid biopsy
Loss of heterozygosity (LOH)
Non-small-cell lung cancer (NSCLC)
Aged
Cell-Free Nucleic Acids
ErbB Receptors
Female
Humans
Middle Aged
Mutation
Proto-Oncogene Proteins p21(ras)
General Medicine
epidermal growth factor receptor (EGFR)
Computer Science Applications
loss of heterozygosity (LOH)
030220 oncology & carcinogenesis
KRAS
medicine.medical_specialty
non-small-cell lung cancer (NSCLC)
Catalysis
Article
Inorganic Chemistry
03 medical and health sciences
Internal medicine
medicine
cell-free DNA (cfDNA)
Physical and Theoretical Chemistry
Lung cancer
Molecular Biology
neoplasms
liquid biopsy
business.industry
Carcinoma
Organic Chemistry
Cancer
medicine.disease
respiratory tract diseases
030104 developmental biology
biology.protein
business
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Volume :
- 21
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....799e644c6ec5f9c43dcd0d72dde9be58