Persistence or de novo occurrence of the KRAS aberration at myeloma relapse and prognostic impact of KRAS in MM. (A) Pie chart of KRAS mutation dynamics in MM patients (n = 27) with serial sampling of relapsed phases. Distribution of KRAS mutations as either appearing mutations or stable. (B) Plot of KRAS tumor fraction trend. Each plot represents a patient. The x-axis shows the stage of sampling (1 = diagnosis and 2-5 = relapse). The y-axis represents the tumor fraction. (C) Heatmap showing KRAS expression levels in relapsed/refractory (RR) MM patients (green). Yellow and purple squares represent the presence or absence, respectively, of expression of the mutation in RNA, and the square size is proportional to its tumor fraction in DNA. (D) Stacked bar chart showing, for KRAS (left) and all other mutations in the RR MM cohort (right), the proportion of mutations that are expressed (green) and not expressed in the presence of gene expression (yellow) and how many genes are not expressed altogether (blue). (E) Kaplan-Meier curves showing the prognostic impact of KRAS in term of OS using the CoMMpass data set. The log-rank test was used to compute P value. First through fourth quartiles are represented in blue, green, red, and dark yellow, respectively. (F) Gene network plot representing pathways significantly upregulated in the fourth KRAS expression quartile compared with the first. Brown dots represent the pathway, with diameter proportional to the size; small dots represent the genes, with each color coded based on its fold change.