Table 2.

The new molecular-based classification of GC according to The Cancer Genome Atlas (TCGA) 2014 and The Asian Cancer Research Group (ACRG) 2015.

TCGA	Epstein–Barr virus-infected (EBV)	Microsatellite instability (MSI)	Genomically stable (GS)	Chromosomal instability (CIN)
	• EBV-positive • Profound hypermethylation • CDKN2A silencing • 80% PIK3CA mutation • PD-L1/2 overexpression • Immune cell signalling • Frequent ARID1A and • BCOR mutations • Fundus and body	• Hypermutation • DNA hypermethylation • Silencing of MLH1 • Elevated somatic mutations (PIK3CA, 42%; ERBB3, 26%) • Older patients • Fundus, body and antrum	• Tumours lacking aneuploidy and elevated rates of mutation or hypermethylation • Somatic RHOA and CDH1 mutations • CLDN18–ARHGAP6 or ARHGAP26 fusions • Mostly diffuse subtype	• Marked aneuploidy • TP53 mutations • Recurrent amplifications of receptor tyrosine kinases (HER2, 24%) • Majority of tumours at the esophagogastric junction
ACRG	MSS/TP53-	MSI	MSS/EMT	MSS/TP53
	Intact TP53 • MDM2 amplification • EBV infection • Enrichment with PIK3A or ARID1A mutation and cytokine signature in EBV-positive tumours	• Hypermutation • Silencing of MLH1 • Frequent mutations in KRAS, MTOR, PIK3CA, ASL and ARID1A • Best prognosis	• CDH1 silencing • Younger patients • Worst prognosis	• TP53 mutation • Genomic instability • Recurrent amplification (ERBB2, EGFR, GATA6, MYC, CCNE1 and CCND1)