Table 1. Genetic background of drug activity determinants in MPM cells.
| NCI-H2052 | NCI-H2452 | NCI-H28 | MSTO-211H | |
|---|---|---|---|---|
| Polymorphisms | ||||
| AKT1-SNP4 | G/G | A/A | G/G | G/G |
| MTHFR-C677T | T/T | C/T | C/C | C/T |
| RFC-A80G | A/A | A/G | A/A | A/A |
| ERCC1-C118T | C/T | T/T | C/T | C/T |
| XPD-Asp312Asn | Asp/Asn | Asp/Asp | Asp/Asp | Asp/Asn |
| XPD-Lys751Gln | Lys/Gln | Lys/Lys | Lys/Lys | Lys/Gln |
| mRNA expression a | ||||
| EGFR | 30.6±2.6 | 75.8±6.1 | 61.9±5.0 | 45.6±3.3 |
| VEGFR-2 | 0.4±0.1 | 2.7±1.0 | nd | 0.9±1.3 |
| RET | 0.5±0.1 | 1.1±0.2 | nd | nd |
| ERCC1 | 7.7±0.8 | 0.3±0.1 | 0.6±0.1 | 2.3±0.4 |
| XPD | 22.4±3.7 | 11.4±1.9 | 8.9±1.4 | 17.5±1.8 |
| TS | 57.7±5.9 | 31.3±3.7 | 106.6±9.4 | 76.7±6.3 |
| E2F-1 | 18.3±2.1 | 13.0±0.9 | 54.3±6.2 | 25.7±2.8 |
| DHFR | 48.2±3.9 | 22.7±1.2 | 27.5±4.5 | 21.0±2.0 |
| GARFT | 1.1±0.1 | 1.8±0.2 | 9.8±0.8 | 3.3±0.5 |
| RFC | 8.4±2.5 | 1.3±0.1 | 1.4±0.3 | 9.5±0.8 |
| FPGS | 53.7±5.6 | 11.1±1.7 | 23.5±2.3 | 55.2±1.6 |
Abbreviations: DHFR=dihydrofolate reductase; EGFR=epidermal growth factor receptor; ERCC1=excision-repair cross-complementing-group-1; FPGS=folyl-polyglutamate synthetase; GARFT=glycinamide ribonucleotide formyltransferase; MPM=malignant pleural mesothelioma; MTHFR=methylene-tetrahydrofolate reductase; nd=not detectable; RFC=reduced folate carrier; TS=thymidylate synthase; Wt=wild-type; XPD=xeroderma-pigmentosum group-D; VEGFR=vascular endothelial growth factor receptor; cDNA=complementary DNA.
a
Relative mRNA expression levels were expressed in arbitrary units and normalised to β-actin, using a method with standard curves derived from serial dilutions from a reference cDNA obtained from Quantitative-PCR Human-Reference Total-RNA.