Figure 2.

Molecular characteristics of early-onset (age <50 years) and average-onset (age ≥50 years) esophagogastric cancer. A) Oncoprint demonstrates that the most frequent oncogenic alterations were similar across the early-onset and average-onset groups (n = 196 early onset, n = 706 average onset). The genes that were altered at a statistically significantly higher frequency in the early-onset group compared with the average-onset group were CCNE1 (16% vs 7%, P = .001, Q = 0.011) and CDH1 (12% vs 6%, P = .004, Q = 0.03). B) Comparison of the tumor mutational burden (mutations/megabase), fraction genome altered, and The Cancer Genome Atlas molecular subtypes demonstrates statistically significantly lower tumor mutational burden and fraction genome altered in the early-onset group than in the average-onset group (tumor mutational burden median = 3.3 vs 4.9 mutations/megabase, P < .001; fraction genome altered median = 0.055 vs 0.132, P < .001) and a higher predominance of the genomically stable subtype. C) Comparison of the frequency of gene- and pathway-level alterations after restricting to adenocarcinoma and signet ring cell/diffuse–type tumors. CDKN2A was found to be statistically significantly enriched in average-onset tumors, whereas CCNE1 and CDH1 were enriched in early-onset tumors. D) Germline genomic analysis using a 76- to 88-gene panel showed that patients in both groups were similarly likely to have high or moderate penetrance alterations (9.9% vs 9.6%, P  > .99). CIN = chromosomal instability; EBV = Epstein-Barr virus; GEJ = gastroesophageal junction; GS = gastric cancer; MSI = microsatellite instability; MSS = microsatellite stabile; NOS = not otherwise specified; ∗= P < .001.