Landscape of RAS variations in 17993 solid tumors: A pan-cancer analysis.

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e15615 Background: RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker. It would also be a promising drug target. AMG 510 which targeting KRAS G12C showed an ORR of 48% in patients with NSCLC. Several trials which evaluating the efficacy of RAS G12C inhibitor in solid tumors are initiated. Herein, we analyzed the alterations status of KRAS/NRAS/HRAS across diverse solid tumors. Methods: The sing nucleotide variants (SNV) and copy number variants (CNV) data of 17993 Chinese patients from 22 types of cancer were obtained in 3DMed database. Genomic profiling of DNA was performed through a next-generation sequencing with 61 cancer-related genes on tissue. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis. Results: Among 17993 pan-cancer patients, the total RAS variants frequency was 23.09%. KRAS was the most frequently altered (90.76% of RAS SNV, 84.70% of RAS CNV), followed by NRAS (6.56% of RAS SNV, 8.58% of RAS CNV) and HRAS (2.68% of RAS SNV, 6.72% of RAS CNV). For the SNV, KRAS were most commonly found in pancreas cancer (685/842, 81.35%), intestine cancer (85/175, 48.57%) and colorectal cancer (1609/3329, 48.33%). NRAS occurred most frequently in melanoma (31/196, 15.82%), colorectal cancer (116/3329, 3.48%) and thyroid cancer (2/60, 3.33%). HRAS were most often found in bladder/urinary tract cancer (46/367, 12.53%), prostate cancer (5/137, 3.65%) and head and neck cancer (7/314, 2.23%). Further analysis among KRAS SNV patients showed that the mutation frequency of KRAS G12C, G12D, G12R and G12V was 9.24%, 34.73%, 3.54% and 21.66%, respectively. A total of 21 in 22 types of solid tumors had KRAS G12C/D/R/V pathogenic or likely pathogenic mutation, which occurred most frequently in colorectal cancer, pancreas cancer and lung cancer. Conclusions: Our results suggested that a variety of solid tumors may harbor KRAS G12C/D/R/V mutation. These patients may benefit from KRAS inhibitors.