Comprehensive characterization of KRAS mutations and inter-relation with primary tumor location in colorectal cancers

Autor: Mohamed E. Salem, Scott Kopetz, Josep Tabernero, Frank A. Sinicrope, Myriam Chalabi, Jeanne Tie, Kunal C. Kadakia, Thomas J. George, Elizabeth Mauer, Lisa Macera, Calvin Y. Chao, Sara Lonardi, Eric Van Cutsem, Thierry Andre, Michael J. Overman
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Oncology. 41:231-231
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2023.41.4_suppl.231
Popis: 231 Background: The recent development of KRAS G12C inhibitors underscores the potential to target KRAS mutations. Right-sided and left-sided colon tumors (RT and LT) exhibit different molecular features. We characterize the prevalence of KRAS-variants, interrelation with primary tumor location, and association with immune biomarkers in CRC. Methods: We retrospectively reviewed CRC tumors of all stages (with known sidedness) that underwent NGS with the Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq). Bivariate analyses were performed to compare KRAS alterations, immune biomarkers, and co-mutations by tumor location. P-values comparing individual co-mutations between groups were adjusted for false discovery (FDR). Results: A total of 3,391 CRC were analyzed (RT: n = 442 [13%], transverse: n = 116 [3%], LT; n = 2,833 [84%]) of which 1486 (44%) tumors harbored KRAS mutations. Overall, KRAS mutations were more frequent in RT compared to transverse tumors and LT (52% vs 41% vs 43%, p10 mut/mb) status than LT (MSI-H: 18% vs 22% vs 2.2% and TMB-H (20% vs 22% vs 3%, P
Databáze: OpenAIRE
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