Intratumor heterogeneity and tissue distribution of KRAS mutation in non-small cell lung cancer: implications for detection of mutated KRAS oncogene in exhaled breath condensate
Open accessAbstract
PURPOSE: Mutated KRAS oncogene in exhaled breath condensate (EBC) can be a genetic marker of non-small cell lung cancer (NSCLC). However, a possibility of inhomogeneous distribution in cancer tissue and intratumor heterogeneity of KRAS mutation may decrease its significance. We investigated a status of KRAS point mutation and its sequence at codon 12 in 51 NSCLC patients after tumor resection. The comparison of KRAS mutation status between EBC-DNA and cancer tissue was performed in 19 cases. METHODS: Five cancer tissue samples from disparate tumor regions and one from normal lung were harvested at surgery. EBC was collected for DNA analysis the previous day. KRAS point mutations at codon 12 were detected using mutant-enriched PCR technique and pyrosequenced. RESULTS: Forty-six cancers revealed concordance of KRAS mutation status: 27 contained mutated KRAS and 19 had only wild KRAS. Five NSCLCs revealed inhomogeneous distribution of KRAS mutation. Two different mutations were found in 14 NSCLCs and the most frequent one was G12D and G12V (n = 8). No mutated KRAS was found in normal lung. The concordance ratios of KRAS sequence in codon 12 between EBC-DNA and cancer were 18/19 for NSCLC patients and 11/12 for KRAS mutation positive NSCLC. CONCLUSIONS: Intratumor heterogeneity and inhomogeneous distribution of KRAS point mutation in codon 12 in cancer tissue can occur in NSCLCs. There was a high accordance between KRAS mutation status in EBC-DNA and cancer tissue in NSCLC patients what suggests usefulness of monitoring KRAS mutation in EBC-DNA as a biomarker of NSCLC.
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Mutation status of KRAS gene could be heterogeneous in the same patient, leading to heterogeneous responses to K-RasG12C inhibition across individuals and in different tumors of the same patient.
“Notably, the mutation status of KRAS gene could be heterogeneous in the same patient, which leads to the heterogeneous responses to K-RasG12C inhibition across individuals, as well as in different tumors of the same patient (Figure 3E).70,71”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [70]
Intratumoral KRAS mutation status could be heterogeneous between primary tumor and metastases in the same patient.
“Given that intratumoral KRAS mutation status could be heterogeneous between primary tumor and metastases in the same patient,70 immunological memory induced by combinatory K-RasG12C and checkpoint inhibition would be beneficial for patients across all stages of cancer (Table 3).”
From Overcoming Resistance to Drugs Targeting KRAS Mutation (2020) · cites this paper as [70]
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- Authors
- Kordiak, J., Szemraj, J., Grabska-Kobylecka, I., Bialasiewicz, P., Braun, M., Kordek, R., & Nowak, D.
- Affiliations
- Medical University of Lodz (PL)
- Corresponding author
- Nowak, Dariusz
- Venue
- Journal of Cancer Research and Clinical Oncology
- Published
- 2018-10-27
- Volume
- 145
- Issue
- 1
- Pages
- 241-251
- ISSN
- 0084-5353 (ISSN-L)
- 0171-5216
- 1432-1335
- PMC
- PMC6325989
- OpenAlex
- W2898144613
- Cited by
- 38
- References
- 36
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 1
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cancer Research and Clinical Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Science Centre Poland (402-350-838)
- Uniwersytet Medyczny w Lodzi (503/5-138-01/503-01, 503/6-086-01/503-61-001, 503/1-079-01/503-11-001, 503/1-079-06/503-11-001, 503/1-034-03/503-11-001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- KRAS mutation, non-small cell lung cancer, intratumoral heterogeneity, exhaled breath condensate, liquid biopsy, codon 12, G12D, G12V, tumor markers
- MeSH terms
- Adenocarcinoma of Lung, Aged, Bayes Theorem, Breath Tests, Carcinoma, Squamous Cell, Codon, DNA, Neoplasm, Female, Genetic Markers, Humans, Lung Neoplasms, Male, Middle Aged, Prospective Studies, Genes, ras, Biomarkers, Tumor, Polymerase Chain Reaction, Point Mutation
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