The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies
Abstract
:1. Introduction
2. Results
2.1. c-Met Expression and Gene Amplification
2.2. c-Met Primary Tumor Versus Metastasis
2.3. Correlation between c-Met and EGFR
2.4. c-Met and TP53 Mutations
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. IHC and CISH
4.3. EGFR-Mutation Analysis
4.4. Next Generation Sequencing
4.5. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Mutation | RefSNP | Allelic Balance (%) | MAF | Reads on Position | c-Met-IHC | Histology |
---|---|---|---|---|---|---|
N375S | rs33917957 | 61 | 2.3% | 10230 | 1+ | Adeno |
E168D | rs55985569 | 50 | 0.5% | 4659 | 3+ | Adeno |
S203T | rs200861145 | 12 | 0.1% | 2093 | 2+ | Squamous |
S203T | rs200861145 | 11 | 0.1% | 2709 | 2+ | Adeno |
S203T | rs200861145 | 15 | 0.1% | 5209 | 1+ | Squamous |
S203T | rs200861145 | 14 | 0.1% | 4590 | 2+ | Squamous |
S203T | rs200861145 | 20 | 0.1% | 1816 | 2+ | Adeno |
E168D | rs55985569 | 43 | 0.5% | 9341 | 3+ | Adeno |
I333T | NA | 8 | NA | 7765 | 3+ | Squamous |
G783E | NA | 11 | NA | 1061 | 3+ | Squamous |
S203T | rs200861145 | 45 | 0.1% | 6009 | 2+ | Adeno |
C3082+1G>T | rs869320707 | 12 | 0% | 1353 | 2+ | Adeno |
C2942−1G>A | NA | 39 | NA | 1180 | 3+ | Adeno |
Sample ID | WT Codon | Mutant Codon | p.Mutant | c.Mutant | Functionality | c-Met | EGFR |
---|---|---|---|---|---|---|---|
8 | TGC | TTC | p.C242F | c.725G>T | Partial function Non-functional | 3+ | WT |
9 | GGG | TGG | p.G334W | c.1000G>T | Partial function | 1+ | WT |
10 | CGC | CTC | p.R337L | c.1010G>T | Non-functional | 2+ | WT |
17 | AGG | ATG | p.R249M | c.746G>T | Non-functional | 3+ | WT |
18 | CCT | TCT | p.P278S | c.832C>T | Non-functional | 2+ | L858R |
19 | GTC | GAC | p.V157D | c.470T>A | Non-functional | 2+ | WT |
58 | GAA | CAA | p.E258Q | c.772G>C | Partial function | 1+ | NA |
59 | AGG | ACG | p.R249T | c.746G>C | Non-functional | 2+ | NA |
72 | CGC | CTC | p.R175L | c.524G>T | Partial function | 0 | NA |
74 | CGA | TGA | p.R342X | c.1024C>T | NA | 2+ | NA |
75 | AGA | GGA | p.R280G | c.838A>G | Partial function Non-functional | 1+ | NA |
79 | GAC | CAC | p.D281H | c.841G>C | Non-functional | 0 | WT |
80 | GAG | AAG | p.E285K | c.853G>A | Non-functional | 2+ | NA |
81 | GCC | CCC | p.A276P | c.826G>C | Non-functional | 2+ | NA |
85 | GGG | GTG | p.G334V | c.1001G>T | Partial function | 3+ | NA |
92 | CGC | CAC | p.R158H | c.473G>A | Non-functional | 3+ | NA |
94 | CGT | CTT | p.R273L | c.818G>T | Non-functional | 1+ | NA |
97 | AGA | GGA | p.R280G | c.838A>G | Non-functional | 2+ | L858R |
97 | GGA | GTA | p.G266V | c.797G>T | Non-functional | 2+ | L858R |
97 | GGC | TGC | p.G245C | c.733G>T | Non-functional | 2+ | L858R |
101 | CGG | CAG | p.R267Q | c.800G>A | Partial function | 0 | NA |
101 | CCT | TCT | p.P190S | c.568C>T | Partial function | 0 | NA |
103 | GGT | GTT | p.G262V | c.785G>T | Non-functional | 1+ | NA |
104 | CGT | CCT | p.R273P | c.818G>C | Non-functional | 3+ | L858R |
105 | AAG | AGG | p.K132R | c.395A>G | Partial function Non-functional | 1+ | NA |
117 | GGA | GTA | p.G266V | c.797G>T | Non-functional | 1+ | NA |
118 | GAG | TAG | p.E294X | c.880G>T | NA | 0 | NA |
121 | CCT | ACT | p.P278T | c.832C>A | Non-functional | 1+ | NA |
128 | GTG | GGG | p.V216G | c.647T>G | Non-functional | 2+ | NA |
131 | CGA | TGA | p.R196X | c.586C>T | NA | 0 | NA |
133 | CCC | TCC | p.P151S | c.451C>T | Non-functional | 0 | NA |
136 | GAG | TAG | p.E298X | c.892G>T | NA | 2+ | NA |
137 | CAT | CGT | p.H179R | c.536A>G | Partial function Non-functional | 2+ | NA |
141 | CAT | CGT | p.H214R | c.641A>G | Non-functional | 2+ | WT |
149 | CGT | CTT | p.R273L | c.818G>T | Non-functional | 3+ | WT |
153 | CAG | TAG | p.Q192X | c.574C>T | NA | 2+ | L858R |
160 | AGA | GGA | p.R280G | c.838A>G | Partial function Non-functional | 2+ | WT |
Age | Range: 36–78 Years (Mean: 62) | N |
---|---|---|
Histology | Adenocarcinoma | 104 |
Squamous carcinoma | 38 | |
Large cell (or not otherwise specified, NOS) | 11 | |
Differentiation | Well | 32 |
Moderate | 63 | |
Poor | 26 | |
Invasiveness | Non-invasive | 49 |
Invasive | 102 | |
Gender | Male | 109 |
Female | 44 | |
Smoking | Non-smoker | 61 |
Smoker | 92 |
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Van Der Steen, N.; Zwaenepoel, K.; Mazzaschi, G.; A. Luirink, R.; P. Geerke, D.; Op de Beeck, K.; Hermans, C.; Tiseo, M.; Van Schil, P.; Lardon, F.; et al. The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies. Molecules 2019, 24, 4443. https://doi.org/10.3390/molecules24244443
Van Der Steen N, Zwaenepoel K, Mazzaschi G, A. Luirink R, P. Geerke D, Op de Beeck K, Hermans C, Tiseo M, Van Schil P, Lardon F, et al. The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies. Molecules. 2019; 24(24):4443. https://doi.org/10.3390/molecules24244443
Chicago/Turabian StyleVan Der Steen, Nele, Karen Zwaenepoel, Giulia Mazzaschi, Rosa A. Luirink, Daan P. Geerke, Ken Op de Beeck, Christophe Hermans, Marcello Tiseo, Paul Van Schil, Filip Lardon, and et al. 2019. "The Role of c-Met as a Biomarker and Player in Innate and Acquired Resistance in Non-Small-Cell Lung Cancer: Two New Mutations Warrant Further Studies" Molecules 24, no. 24: 4443. https://doi.org/10.3390/molecules24244443