Introduction
Materials and methods
Study population
Demographic/clinical variable | Patients with non-small cell lung cancer | ||
---|---|---|---|
Squamous cell carcinoma | Adenocarcinoma | Whole group | |
Number | 32 | 16 | 51b |
Sex F/M | 15/17 | 6/10 | 24/27 |
Age (years) | 67 ± 8 | 66 ± 8 | 66 ± 8 |
Surgery Pn/Bl/Lo | 7/0/25 | 3/4/9 | 12/4/35 |
Cs/Fs/Ns | 15/13/4 | 8/5/3 | 25/18/8 |
Pack-yearsa | 38 ± 20 | 40 ± 21 | 39 ± 20 |
Study protocol
Demographic/clinical variable | Patients with non-small cell lung cancer | ||
---|---|---|---|
Squamous cell carcinoma | Adenocarcinoma | Whole group | |
Number | 9 | 7 | 19b |
Sex F/M | 5/4 | 2/5 | 10/9 |
Age (years) | 67 ± 10 | 70 ± 6 | 67 ± 9 |
Surgery Pn/Bl/Lo | 1/0/8 | 2/1/4 | 5/1/13 |
Cs/Fs/Ns | 4/4/1 | 3/3/1 | 9/7/3 |
Pack-yearsa | 31 ± 17 | 38 ± 20 | 35 ± 17 |
Collection of exhaled breath condensate (EBC) and blood samples
DNA extraction and detection of KRAS oncogene point mutations at codon 12
Sequence analysis of KRAS oncogene mutations
Statistical analysis
Results
KRAS mutation status in NSCLC samples
Fraction of KRAS mutation positive cancer samples | Number of NSCLC patients | Histological diagnosis | KRAS mutation distribution over the cancer tissue | |
---|---|---|---|---|
SSC/ADC/ADSCC/LCNEC | Homogeneous | Inhomogeneous | ||
5/5 | 27 | 16/10/0/1 | 27 | 0 |
4/5 | 2 | 0/2/0/0 | 0 | 2 |
3/5 | 1 | 0/0/0/1 | 0 | 1 |
2/5 | 1 | 0/1/0/0 | 0 | 1 |
1/5 | 1 | 0/0/1/0 | 0 | 1 |
Overall | 32 | 16/13/1/2 | 27 | 5 |
Variability of mutated sequences of KRAS oncogene point mutations at codon 12 in NSCLCs samples
Number of patients | Fraction of KRAS mutation positive cancer tissue samples | Histological diagnosis SCC/ADC/LCNEC | Number of identified KRAS point mutations in KRAS mutation positive cancer tissue samples | ||||
---|---|---|---|---|---|---|---|
G12D | G12V | G12C | G12A | G12S | |||
Patients presenting with intratumor heterogeneity of KRAS oncogene point mutations (n = 14) | |||||||
5 | 5/5 | 2/3/0 | 2 | 3 | 0 | 0 | 0 |
3 | 5/5 | 3/0/0 | 3 | 2 | 0 | 0 | 0 |
2 | 5/5 | 2/0/0 | 0 | 3 | 2 | 0 | 0 |
2 | 5/5 | 2/0/0 | 2 | 0 | 3 | 0 | 0 |
1 | 5/5 | 1/0/0 | 2 | 0 | 0 | 0 | 3 |
1 | 5/5 | 0/1/0 | 1 | 0 | 4 | 0 | 0 |
Patients not presenting with intratumor heterogeneity of KRAS oncogene point mutations (n = 17) | |||||||
10 | 5/5 | 4/5/1 | 5 | 0 | 0 | 0 | 0 |
2 | 5/5 | 1/1/0 | 0 | 0 | 0 | 5 | 0 |
1 | 5/5 | 1/0/0 | 0 | 5 | 0 | 0 | 0 |
2 | 4/5 | 0/2/0 | 4 | 0 | 0 | 0 | 0 |
1 | 3/5 | 0/0/1 | 3 | 0 | 0 | 0 | 0 |
1 | 2/5 | 0/1/0 | 2 | 0 | 0 | 0 | 0 |
Between-sample comparison of point mutations sequence at codon 12 in NSCLCs harboring mutated KRAS oncogene
Occurrence of KRAS mutated gene in blood and EBC samples in relation to KRAS mutation status in NSCLC tissue samples
Patient number and diagnosis | Identified KRAS point mutations | Number of discrepancies | ||||
---|---|---|---|---|---|---|
EBC | Blood | Cancer tissue samplesa | EBC versus blood | EBC versus tumor | Blood versus tumor | |
1. SCC | G12D | (–) | 3 G12D, 2 G12V | 1 | 0 | 1 |
2. SCC | G12D | (–) | 5 G12D | 1 | 0 | 1 |
3. SCC | (–) | G12C | 3 G12V, 2 G12C | 1 | 1 | 0 |
4. SCC | (–) | G12D | 5 (–) | 1 | 0 | 1 |
5. ADC | G12D | G12D | 5 G12D | 0 | 0 | 0 |
6. ADC | G12D | G12V | 5 G12D | 1 | 0 | 1 |
7. ADC | G12D | (–) | 3 G12V, 2 G12D | 1 | 0 | 1 |
8. ADC | G12D | G12D | 5 G12D | 0 | 0 | 0 |
9. ADC | G12D | (–) | 4 G12D, 1 (–) | 1 | 0 | 1 |
10. ADC | G12D | (–) | 2 G12D, 3 (–) | 1 | 0 | 1 |
11. ADC | (–) | G12D | 5 (–) | 1 | 0 | 1 |
12. ADSCC | G12D | G12V | 1 G12D, 4 (–) | 1 | 0 | 1 |
13. LCNEC | G12D | G12D | 5 G12D | 0 | 0 | 0 |
14. LCNEC | G12D | G12D | 3 G12D, 2 (–) | 0 | 0 | 0 |
Overall | 10 | 1 | 9 |