Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Sample Selection
2.3. Sample Analysis
2.4. Whole Exome Capture and Sequencing
2.5. Exome Analysis Pipeline
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Analysis of Genomic Scores
3.3. Analysis of Mutational Signatures
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variables | Whole Cohort N = 132 |
---|---|
Age | 64 (58, 72) |
Unknown | 23 |
Sex | |
Male | 62 (57%) |
Female | 47 (43%) |
Unknown | 23 |
Smoking status | |
Never smoker | 15 (15%) |
Current smoker | 35 (34%) |
Former smoker | 52 (51%) |
Unknown | 30 |
WHO performance status | |
0 | 16 (15%) |
1 | 62 (58%) |
2 | 24 (23%) |
3 | 4 (3.8%) |
Unknown | 26 |
Brain metastasis | |
0 | 79 (72%) |
1 | 31 (28%) |
Unknown | 22 |
Lymph node metastasis | |
0 | 22 (20%) |
1 | 88 (80%) |
Unknown | 22 |
Lung metastasis | |
0 | 86 (78%) |
1 | 24 (22%) |
Unknown | 22 |
Bone metastasis | |
0 | 58 (53%) |
1 | 52 (47%) |
Unknown | 22 |
PDL1 (cutoff at 50%) | |
<50% | 69 (62%) |
≥50% | 43 (38%) |
Unknown | 20 |
Histological type | |
Adenocarcinoma | 95 (73%) |
Carcinoma | 16 (12%) |
Other | 20 (15%) |
Unknown | 1 |
Histological type | |
Squamous | 16 (12%) |
Non-squamous | 115 (88%) |
Unknown | 1 |
Treatments | |
Chemotherapy | 40 (43%) |
Chemoimmunotherapy | 28 (30%) |
Immunotherapy | 9 (9.6%) |
Targeted therapy | 17 (18%) |
Unknown | 38 |
Response | |
Complete response | 9 (7%) |
Partial response | 51 (44%) |
Stable disease | 26 (22%) |
Progressive disease | 30 (26%) |
Unknown | 16 |
Variables | Whole Cohort N = 132 |
---|---|
TMB score | 6.9 (4.3, 10.8) |
Unknown | 14 |
Number of neoantigens/Mb | 9 (6, 17) |
Unknown | 17 |
Number of strong neoantigens/Mb | 1 (0, 3) |
Unknown | 17 |
TCR clonality | 1 (0, 2) |
KRAS/EGFR mutation | |
KRAS G12C | 15 (11%) |
Other KRAS | 24 (18%) |
EGFR | 12 (9.1%) |
No mutation | 81 (61%) |
HRD score | 32 (22, 42) |
Unknown | 13 |
MSI score | 0.08 (0.00, 1.15) |
Unknown | 14 |
CNA score | 0.25 (0.09, 0.40) |
Unknown | 13 |
Variables | Univariate | Multivariate | ||||
---|---|---|---|---|---|---|
HR | 95%CI | p-Value | HR | 95%CI | p-Value | |
SBS7a | 1.10 | [1.04; 1.16] | 0.002 | 1.08 | [1.01; 1.14] | 0.02 |
SBS19 | 1.06 | [1.01; 1.11] | 0.013 | 1.07 | [1.02; 1.12] | 0.005 |
SBS24 | 1.01 | [1.00; 1.01] | 0.008 | 1.00 | [0.99; 1.01] | >0.9 |
SBS28 | 1.07 | [1.03; 1.11] | <0.001 | 1.08 | [1.04; 1.12] | <0.001 |
SBS89 | 1.01 | [1.00; 1.01] | <0.001 | 1.01 | [1.00; 1.01] | <0.001 |
DBS6 | 1.24 | [1.05; 1.47] | 0.011 | 1.28 | [1.08; 1.51] | 0.004 |
DBS9 | 1.75 | [1.17; 2.62] | 0.006 | 1.87 | [1.25; 2.81] | 0.002 |
DBS15 | 1.22 | [1.02; 1.46] | 0.032 | 1.25 | [1.05; 1.50] | 0.014 |
Treatment | Chemotherapy | Chemoimmunotherapy | Immunotherapy | Targeted Therapy | |
---|---|---|---|---|---|
Group | |||||
SBSLow | 32 (32%) | 24 (24%) | 5 (5%) | 17 (17%) | |
SBSHigh | 5 (33%) | 4 (27%) | 4 (27%) | 0 (0%) | |
DBSLow | 21 (24%) | 26 (30%) | 6 (7%) | 13 (15%) | |
DBSHigh | 13 (60%) | 2 (9%) | 2 (9%) | 2 (9%) |
Mutation | KRAS G12C | Other KRAS | EGFR | No Mutation | |
---|---|---|---|---|---|
Group | |||||
SBSLow | 12 (12%) | 21 (21%) | 12 (12%) | 56 (56%) | |
SBSHigh | 3 (20%) | 2 (13%) | 0 (0%) | 10 (66%) | |
DBSLow | 11 (12%) | 18 (20%) | 9 (10%) | 50 (57%) | |
DBSHigh | 3 (14%) | 5 (23%) | 2 (9%) | 12 (55%) |
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Peroz, M.; Mananet, H.; Roussot, N.; Kaderbhai, C.G.; Derangère, V.; Truntzer, C.; Ghiringhelli, F. Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer. Cancers 2024, 16, 3115. https://doi.org/10.3390/cancers16173115
Peroz M, Mananet H, Roussot N, Kaderbhai CG, Derangère V, Truntzer C, Ghiringhelli F. Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer. Cancers. 2024; 16(17):3115. https://doi.org/10.3390/cancers16173115
Chicago/Turabian StylePeroz, Morgane, Hugo Mananet, Nicolas Roussot, Courèche Guillaume Kaderbhai, Valentin Derangère, Caroline Truntzer, and François Ghiringhelli. 2024. "Clinical Interest in Exome-Based Analysis of Somatic Mutational Signatures for Non-Small Cell Lung Cancer" Cancers 16, no. 17: 3115. https://doi.org/10.3390/cancers16173115