Table 3. TCGA Subtypes.
Subtypes | EBV-positive | MSI | GS | CIN |
---|---|---|---|---|
Frequency | 8.8% | 21.7% | 19.7% | 49.8% |
Demographic | Male patients (81%) | Old age (median 72 years) | Young age (median 59 years) | No special |
Histology | Diffuse histology | Intestinal histology | ||
Main location | Fundus or body (62%) | Gastro-esophageal junction/cardia (65%) | ||
Molecular alterations | EBV-CpG island methylator phenotype (CIMP) | Gastric-CIMP | CDH1, RHOA mutation | TP53 mutation |
PD-L1/2, JAK2 overexpression | Hypermutation in TP53, PIK3CA, ERBB3, ARID1A | CLDN18-ARHGAP fusion | RTK-RAS activation | |
Mutation in PIK3CA, ARID1A, BCOR | MLH1 silencing | Cell adhesion, angiogenesis pathways enriched | Mutations of SMAD4 and APC | |
CDKN2A silencing | Mitotic pathways activation | Rare TP53 mutations | ||
Immune cell signaling | Commune changes in the genes of CMHI | |||
Rare TP53 mutations | ||||
Potential targets | PIK3CA, JAK2, PD-L1/PD-L2 | PIK3CA, ERBB2/3, EGFR, PD-L1, MLH1 silencing | RHOA, CLDN18 | RTKs, EGFR, VEGFA, CCNE1, CCND1, CDK6 |
Treatment reaction | No respond to adjuvant chemotherapy |
ARID1A: AT-rich interactive domain-containing protein 1A; BCOR: B-cell lymphoma 6 corepressor; CIN: chromosomal instability; GS: genomically stable; GC: gastric cancer; CIMP: CpG island methylator phenotype; DNMT3b: DNA methyltransferase 3b; EBV: Epstein-Barr virus; EGFR: epithelial growth factor receptor; ERBB2: Erb-B2 receptor tyrosine kinase 2; JAK2: Janus-associated kinase 2; LMP2A: latent membrane protein 2A; LELC: lymphoepithelioma-like carcinoma; MSI: microsatellite instability; PI3K: phosphatidylinositol-3-kinase; RHOA: Ras homolog family member A; TCGA: The Cancer Genome Atlas; PD-L1/2: programmed death ligand-1/2; CDK6: cell division protein kinase 6.