Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer.
Mol Cancer Ther
; 20(12): 2577-2584, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34518295
ABSTRACT
KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS-mutated non-small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development.Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of KRAS mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by KRAS mutation type.Across the cohort, 4,706 (27.5%) samples harbored a KRAS mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across KRAS mutation subtypes. KRAS G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). STK11 was mutated in 8.6% of KRAS wild-type NSCLC but more frequent in KRAS-mutant NSCLC, with the highest rate in G13 (36.2%). TP53 mutations were more frequent in KRAS wild-type NSCLC (73.6%).KRAS mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas p21(ras)
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Carcinoma de Pulmón de Células no Pequeñas
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Secuenciación de Nucleótidos de Alto Rendimiento
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Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Cancer Ther
Asunto de la revista:
ANTINEOPLASICOS
Año:
2021
Tipo del documento:
Article