RESUMEN
BACKGROUND: KRAS is mutated in â¼30% of non-small-cell lung cancer (NSCLC) but it has also been identified as one of the mechanisms underlying resistance to tyrosine kinase inhibitors (TKIs) in EGFR-positive NSCLC patients. Novel KRAS inhibitors targeting KRAS p.G12C mutation have been developed recently with promising results. The proportion of EGFR-positive NSCLC tumours harbouring the KRAS p.G12C mutation upon disease progression is completely unexplored. MATERIALS AND METHODS: Plasma samples from 512 EGFR-positive advanced NSCLC patients progressing on a first first-line treatment with a TKI were collected. The presence of KRAS p.G12C mutation was assessed by digital PCR. RESULTS: Overall, KRAS p.G12C mutation was detected in 1.17% of the samples (n = 6). In two of these cases, we could confirm that the KRAS p.G12C mutation was not present in the pre-treatment plasma samples, supporting its role as an acquired resistance mutation. According to our data, KRASG12C patients showed similar clinicopathological characteristics to those of the rest of the study cohort and no statistically significant associations between any clinical features and the presence of the mutation were found. However, two out of six KRASG12C tumours harboured less common EGFR driver mutations (p.G719X/p.L861Q). All KRASG12C patients tested negative for the presence of p.T790M resistance mutation. CONCLUSIONS: The KRAS p.G12C mutation is detected in 1% of EGFR-positive NSCLC patients who progress on a first line with a TKI. All KRASG12C patients were negative for the presence of the p.T790M mutation and they did not show any distinctive clinical feature.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/genéticaAsunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Supervivencia de Injerto/efectos de los fármacos , Interleucina-15/farmacología , Movimiento Celular/efectos de los fármacos , Células Clonales/efectos de los fármacos , Humanos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacosRESUMEN
We have now found a total of 15 individual MICB promoter sequences, varying by combination of 18 polymorphic positions within the MICB minimal promoter sequence. Sequence-based typing and cloning characterized the three new 5' promoter sequences as MICB-P13, MICB-P14 and MICB-P15.
Asunto(s)
Variación Genética , Antígenos de Histocompatibilidad Clase I/genética , Regiones Promotoras Genéticas , Alelos , Haplotipos/genética , Haplotipos/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , HumanosRESUMEN
In this study, we have characterized two novel polymorphism of the 5' promoter sequence of MICA gene, MICA-P13 and MICA-P14, by sequence-based typing and cloning.
Asunto(s)
Antígenos de Histocompatibilidad Clase I/genética , Regiones Promotoras Genéticas , Alelos , Haplotipos , Humanos , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
Description of a novel RAET1E/ULBP4 allele characterized by sequence-based typing and cloning: RAET1E*011.