Molecular characteristics of KRAS mutations in Chinese patients with cancer.

Abstract

e15070 Background: Sotorasib, the first KRAS G12C inhibitor, has been approved for the treatment of non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation-positive. Understanding the molecular characteristics of KRAS in Chinese patients with cancer is imperative, which is conducive to screening the beneficiary groups. Here, we focus on the molecular characterization of KRAS in NSCLC, colorectal cancer (CRC), pancreatic cancer (PC), and gastric cancer (GC). Methods: This study enrolled 17,775 pan-cancer patients detected by next-generation sequencing (NGS) from June 2021 to February 2022, in which NSCLC, CRC, PC and GC were 48.67% (8651/17775), 10.87% (1933/17775), 1.92% (342/17775) and 5.37% (955/17775), respectively. Results: The KRAS mutation rate in pan-cancer is 16.28% (2893/17775). In NSCLC, CRC, PC and GC cohorts, the mutation rates of KRAS were 13.28% (1149/8651), 50.34% (973/1933), 66.67% (228/342) and 7.64% (73/955), respectively. In NSCLC cohort, 1274 KRAS mutations were detected, and the subtypes were concentrated in G12C (346;27.16%), G12D (205;16.10%), G12V (194;15.23%), G12A (86;6.75) and Q61H (57;4.47%). In CRC cohort, 1094 KRAS mutations were detected. The subtypes were mainly distributed in G12D (350;31.40%), G13D (184;16.82%), G12V (180;16.45%), A146P (66;6.03%) and G12C (49;4.48%). In PC cohort, 251 KRAS mutations were detected, and the subtypes were concentrated in G12D (109;43.43%), G12V (70;27.89%), G12R (32;12.75%), G12C (9;3.59%) and Q61H (9;3.59%). In GC cohort, 82 KRAS mutations were detected. The subtypes of these mutations were concentrated in G12D (23;28.05%), G13D (12;14.63%), Q61H (7;8.54%), G12V (5;6.10%) and Q61R (5;6.10%). Conclusions: In NSCLC, CRC, PC and GC cohorts, K RAS mutations were concentrated in exon 2, accounting for 78.41% (999/1274), 81.63% (893/1094), 91.63% (230/251) and 64.63% (53/82), respectively. In NSCLC cohort, KRAS G12C was the molecular subtype with the highest mutation rate. However, in other cohorts, KRAS G12D was the predominant molecular subtype. G12D mutation will become the next research hotspot, and the breakthrough will help to further expand the beneficiary population of KRAS mutations.