Table 1.
Cancer | Molecular classes | Salient molecular aberrations | Salient microenvironmental and/or histological features |
---|---|---|---|
PRIMARY BRAIN CANCERS | |||
Pediatric | |||
Medulloblastoma (18) | |||
WNT | Increased WNT signaling | Fenestrated vasculature enabling access of chemotherapy (19) | |
SHH | Increased SHH signaling | Intact BBB that restricts access of chemotherapy (19) | |
3 | MYC amplification | Higher proportion of PD-1+ CD8+ T cells (20) | |
4 | CDK4 and MYCN amplification | ||
Adult | |||
Glioma | |||
HIGH GRADE (WHO grade 4) | |||
Glioblastoma (21–23) | |||
IDHwt | |||
MES | NF-1 loss | Higher macrophage infiltrate (23–26). More CD4 T cells and neutrophils (23). Higher PD-L1 expression (23). | |
CL | EGFR gain and PTEN loss | ||
PN | PDGFRA gain | Associated with lower levels of PD-L1 (23) | |
IDHmut | Blunted T cell abundance and activation (27). Reduced neutrophils (28) and downregulation of NKG2D (29) |
||
PN | IDH mutations | ||
LOW GRADE (WHO grade 1–3) | |||
Astrocytomas | TP53 and ATRX mutations (30) | Microenvironmental signature enriched in macrophage/microglia-associated genes (31) | |
Oligodendrogliomas | TERT promoter mutations and 1p/19q co-deletion (30) | Microenvironmental signature enriched in neuron-associated genes (31) | |
METASTATIC BRAIN CANCERS | |||
Breast cancer | EGFR gain (only HER2+ tumors) | ||
Melanoma | BRAF mutations | Stat3+ pro-tumorigenic astrocytes (32). Communication between astrocytes and tumor cells by extracellular vesicles (33) or cx43-dependent gap junctions (34) |
|
Lung cancer | KRAS mutations, ALK translocation, EGFR amplification |