Abstract 525P
Background
KRAS mutations are commonly observed in solid tumors, while KRAS amplification is a rare event. This study aims to investigate the potential distinctions between KRAS amplification and KRAS mutation in solid tumors.
Methods
The study included 9,782 Chinese patients with solid tumors who underwent next-generation sequencing (NGS) between February 2023 and February 2024. Additionally, Multiplex immunofluorescence staining was performed to investigate tumor immune microenvironment on 657 patients.
Results
Among the pan-solid tumor cohort, KRAS mutations were identified in 21.64% (2,117/9,782) of cases, predominantly detected in pancreatic cancer, colorectal cancer, and biliary tract tumors, with detection rates of 87.50% (442/505), 47.83% (860/1798), and 25.80% (138/535), respectively. The incidence of KRAS amplification was 1.58% (155/9782), primarily detected in ovarian cancer, pancreatic cancer, and gastric cancer, with detection rates of 5.64% (39/691), 3.17% (16/505), and 1.79% (15/836), respectively. In comparison to the KRAS mutation group, Patients with KRAS amplification exhibited a significantly lower incidence of MSI-H (0% vs. 5.29%, p<0.01) but a higher incidence of TMB-H (≥10 Muts/Mb, 34.43% vs. 22.14%, p<0.01) and exhibited a lower number of SNV/indel (median: 13 vs. 8, P<0.0001) but a higher number of copy number variations (median: 4 vs. 0, P<0.0001). KRAS mutation group had a lower proportion of women compared to KRAS amplification (40.77% vs. 49.78%, p=0.03), while there was no significant difference in the proportion aged <60 (39.63% vs. 42.58%, p=0.47). Moreover, we observed no significant difference in the immune microenvironment data between the KRAS amplification group (n=11) and the KRAS mutation group (n=115).
Conclusions
Compared to KRAS mutation, patients with KRAS amplification tended to exhibit MSS but had a higher proportion of TMB-H. The two cohorts differed in terms of cancer predisposition types and gender ratio. it is crucial to incorporate a more diverse range of population data for comprehensive analysis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.