Comprehensive analysis of aberrations in pan-cancer, with a focus on prognostic and therapeutic implications
Background: KRAS is one of the most frequently mutated oncogenes in humans. KRAS aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes. Objectives: We identified features of genetic alterations in KRAS , including single amino acid substituti...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-08-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359251351438 |
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| Summary: | Background: KRAS is one of the most frequently mutated oncogenes in humans. KRAS aberrations play a significant role in various solid tumors, affecting patient prognosis and treatment outcomes. Objectives: We identified features of genetic alterations in KRAS , including single amino acid substitutions and amplifications, based on the results of next-generation sequencing tests in 1667 advanced solid tumor patients. Design: Retrospective cohort study. Methods: Among 1667 patients, 28.1% ( N = 468) had KRAS aberrations (single-nucleotide variant (SNV): N = 438, 26.1%; amplification (copy number variation): N = 48, 2.9%) in metastatic solid tumors. Results: The incidence rate of SNVs was higher in pancreatic cancer ( N = 89, 89.9%) than in other tumors, including colorectal cancer ( N = 259, 47.3%) and small bowel cancer ( N = 4, 40.0%). Most of the mutations were missense mutations ( N = 434, 99.1%). In addition, we examined the specific location of SNVs; the mutational type G12D ( N = 178, 40.6%) was the most frequent, followed by G12V ( N = 95, 21.7%) and G13D ( N = 47, 10.7%). In the survival analysis, the mutational types of G12V and G13D influenced the poor survival of patients (G12V, the mutant type; 245 vs the wild type; 531 days; G13D, the mutant type; 435 vs the wild type; 531 days). Conclusion: In patients with KRAS amplification, the copy number range varied among the tumor types. Bladder cancer (147.9), cholangiocarcinoma (16.2), and gastric cancer (11.0) had relatively high median copy numbers of KRAS . Overall, our data are expected to provide valuable information for patients with various metastatic solid tumors and KRAS aberrations. |
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| ISSN: | 1758-8359 |