Fig. 5: Genomic analyses from serial biopsy samples of HER2-positive gastric cancer patients treated with the first-line quadruplet regimen.

a Spider plot showing patients with HER2 mutations found in serial NGS analyses of primary tumor. Only cases with HER2 mutations and variant allele frequencies (VAFs) with the corresponding patient IDs are shown. b, c Sensitive (b) or resistant (c) sub-clones in which the sub-clone frequency changed over 2-fold in post-progression (Post-PD) samples (n = 10) or on-treatment (On-Tx) samples (n = 9) compared to paired baseline samples (n = 14) are selected per patient. Statistically significant enriched Reactome pathways with the multiple test correction (Benjamini-Hochberg procedure) were retained, and selected enriched Reactome pathways from sensitive or resistant sub-clone genes are also shown. All paired tissue samples are only from the primary tumor (stomach). Only hotspot gene mutations that appeared in more than two samples are shown in the sub-clone frequency graph. X-axis indicated –log10 adjusted P-values and statistical significance is indicated by the vertical dashed line. d, e Representative cases showing sub-clonal evolution by fish plot and corresponding clinicopathologic features and computed tomography or endoscopic images from paired tissue NGS from both primary tumor (stomach) and metastatic liver. Selected hotspot mutations are labeled. Representative case from good responders (n = 11, d) and poor responder (n = 1, e). HER2, human epidermal receptor 2; ERBB2, Erb-B2 receptor tyrosine kinase 2; NGS, next generation sequencing.