Oncogenic subgroups of lung adenocarcinoma (LUAD) are divided into
smaller subsets on the basis of key co-occurring genomic alterations.
Co-mutations constitute major determinants of tumor molecular diversity and can
impact both tumor cell-autonomous and non-cell-autonomous cancer hallmarks;
determine prognosis; predict response to systemic therapies and influence
mechanisms of innate and acquired resistance. For simplicity, only
KRAS and EGFR co-alterations are depicted
graphically. For KRAS-mutant LUADs the previously identified
KL, KP, and KC transcriptome-based subgroups are also indicated67; co-mutations in
LKB1, KEAP1 and ATM are
significantly enriched in the KL subgroup, whereas co-occurring alterations in
TP53 and bi-allelic inactivation of
CDKN2A/CDKN2B are hallmarks of the KP and KC subgroups
respectively. Co-mutations in RBM10 don’t appear to
exhibit predilection for any of the three KRAS transcriptomic
subgroups. It should therefore be noted that several of the reported
co-alterations within oncogene-defined groups are not mutually exclusive.
Although co-mutation-defined cohorts are represented as slices of equal size,
both the spectrum and prevalence of individual co-mutations evolve according to
disease stage, prior treatment exposures, immune editing and the mutational
processes that are operational at each stage of carcinogenesis.