Heavy mutagenesis by tobacco leads to lung adenocarcinoma tumors with KRAS G12 mutations other than G12D, leading KRAS G12D tumors —on average—to exhibit a lower mutation burden

In a recent analysis of lung adenocarcinoma tumor sequences from TCGA [1], Gao et al. [2] observed that tumors with KRAS G12D mutation have significantly lower tumor mutational burden (TMB) than tumors with other common KRAS G12 mutations, such as G12A, G12C, and G12V. With support from PD-L1 expression data, the authors posit that among KRAS G12 variants, G12D has distinct oncogenic effects: “KRAS G12D drives immune suppression and might be a negative predictive biomarker for anti-PD-1/PD-L1 immune checkpoint inhibitors.” However, there has been insufficient data from large cohort studies to verify any heterogeneity among KRAS G12 subtypes [3,4].

Source: Lung Cancer - October 28, 2021 Category: Cancer & Oncology Authors: Chichun Tan, Jeffrey D. Mandell, Krishna Dasari, Vincent L. Cannataro, Jorge A. Alfaro-Murillo, Jeffrey P. Townsend Source Type: research