Table 1.
The Cancer Genome Atlas has presented a thorough depiction of the molecular basis of gastric cancer[25]
Subtypes
|
EBV-positive
|
MSI
|
GS
|
CIN
|
Frequency, % | 8.8 | 21.7 | 19.7 | 449.8 |
Demographic | Male patients (81%) | Old age (median 72 yr) | Young age (median 59 yr) | Not specific |
Histology | Not specific | Not specific | Diffuse | Intestinal |
Main location | Fundus and body | Fundus, body, and antrum | Mostly diffuse subtype | Majority of tumors at the GEJ |
Molecular | EBV-CIMP: (1) PD-L1/2, JAK2 overexpression; (2) Mutation in PIK3CA, ARID1A, and BCOR; (3) CDKN2A silencing; (4) Immune cell signaling; and (5) Rare TP53 mutations | Gastric-CIMP: (1) Hypermutation in TP53, PIK3CA, ERBB2/3, and ARID1A; (2) MLH1 silencing; (3) Mitotic pathways activation; and (4) Commune changes in the genes of CMH1 | (1) CDH1 and RHOA mutation; (2) CLDN18-ARHGAP fusion; (3) Cell adhesion; (4) Angiogenesis pathways enriched; and (5) Rare TP53 mutations | (1) TP53 mutation; (2) RTK-RAS activation; and (3) Mutations of SMAD4 and APC |
alterations | ||||
Potential therapeutic points | (1) PIK3CA; (2) JAK2; and (3) PD-L1/L2 | (1) PIK3CA; (2) ERBB2/3; (3) EGFR; (4) PD-L1; and (5) MLH1 silencing | (1) RHOA; and (2) CLDN18 | (1) RTKs; (2) EGFR; (3) VEGFA; (4) CCNE1; (5) CCND1; and (6) CDK6 |
APC: Adenomatous polyposis coli; ARHGAP: Rho GTPase activating protein; ARID1A: AT-rich interactive domain-containing protein 1A; BCOR: B-cell lymphoma 6 corepressor; CCND1: Cyclin-D1; CCNE1: Cyclin-E1; CDH1: Cadherin 1; CDK6: Cyclin-dependent kinase 6; CDKN2A: Cyclin-dependent kinase inhibitor 2A; CIMP: CpG island methylator phenotype; CIN: Chromosomal instability; CLDN18: Claudin-18; CMH1: Hypertrophic cardiomyopathy-1; GS: Genomically stable; GC: Gastric cancer; EBV: Epstein-Barr virus; EGFR: Epithelial growth factor receptor; ERBB2/3: Erb-b2 receptor tyrosine kinase 2/3; GEJ: Gastroesophageal junction; JAK2: Janus-associated kinase 2; MLH1: MutL protein homolog 1; MSI: Microsatellite instability; PD-L1/2: Programmed death ligand-1/2; PI3K: Phosphatidylinositol-3-kinase; RAS: Rat sarcoma virus; RHOA: Ras homolog family member A; RTKs: Receptor tyrosine kinases; SMAD4: Mothers against decapentaplegic homolog 4; TP53: Tumor protein 53; VEGFA: Vascular endothelial growth factor A.