The landscape of RAS mutations and hotspots in Chinese patients with solid tumors.

Abstract

e15114 Background: As one of the most commonly oncogene, RAS mutations ( HRAS, NRAS, KRAS) have been confirmed closely related to the tumorgenesis and proliferation of solid tumors.Yet a comprehensive analysis of RAS mutations and hotspots in Pan-Cancers of Chinese is lacking. Herein, we firstly report the RAS mutation frequency and hotspots features based on a Chinese pan-cancers database, aiming to evaluate the correlation between RAS mutation status and the clinical implication of human cancers. Methods: This was a retrospective study in patients with solid tumors performed NGS panel based on tissue or blood samples in ChosenMed. A cohort of 5420 samples consisting of 22 solid tumor types from Chinese was analyzed to exhibit the landscape of RAS mutations and hotspots. Results: According to our database, the total mutation frequency of KRAS, NRAS, and HRAS was 17.34% (940/5429) in 22 tumor types, of which pancreatic cancer, bowel cancer and endometrial eancer occurred more commonly (with mutation frequencies of 64.04%, 46.07%, and 26.32%, respectively). The RAS mutation hotspots mainly consisted of G12, G13, and Q61, which exhibited preference in each RAS isoforms. For KRAS, G12 mutation site occupied 76.99% (619/804) of all mutations, and mutations at Q61 accounted for 52.83% (28/53) of NRAS mutations. Lastly, HRAS mutations at above three sites presented lowest proportion of 16.83% (17/101). Conclusions: This study firstly reports the RAS mutation characters in pan-cancers based on the Chinese database, which has provided RAS hotspots details for helping to screen more tumor patients who are sensitive to RAS inhibitors. Also, further investigation should be performed for the development of RAS-targeting drugs.