Table 2.
Vogelstein's pathways and mutation prevalence in the cohort (n = 870)
| Cancer cell signaling pathways/processes | Unique pathway genes | Mutated pathwayd (prevalence in cohort), % | P‐valuee , a (difference across the genomic groups) |
|---|---|---|---|
| Cell fate | |||
| NOTCH | FBXW7, NOTCH1, NOTCH2 | 13 | Not sign |
| HH | PTCH1, SMO | 5 | < 0.001b |
| APC | APC, AXIN1, CDH1, CTNNB1, FAM123B, HNF1A, NF2 | 23 | Not sign |
| Chromatin modification | ARID1A, ARID1B, ATRX, DNMT1, DNMT3A, EXH2, KDM6A, MEN1, MLL2, MLL3, PBRM1, SETD2, SMARCA4, SMARCB1 | 47 | 0.03c |
| Transcriptional regulation | AR, GATA3, RUNX1 | 7 | Not sign |
| Genome maintenance | |||
| DNA damage control | ATM, BAP1, BRCA1, BRCA2, MLH1, MSH2, MSH6 | 21 | Not sign |
| Cell survival | |||
| TGF‐β | ACVR1B, SMAD4) | 2 | Not sign |
| MAPK | GNA11, GNAQ | 4 | 0.04d |
| STAT | JAK1, JAK2, JAK3 | 8 | Not sign |
| PI3K | AKT1, PIK3CA, PIK3R1, PTEN, TSC1 | 16 | 0.002d |
| RAS | BRAF, CIC, HRAS, KRAS, NF1, NRAS, PTPN11 | 89 | Not sign |
| Cell cycle/Apoptosis | ABL1, BCL2, CASP8, CDC73, CDKN2A, CYLD, RB1, TRAF7 | 24 | 0.008e |
Non‐synonymous mutations in any of the genes.
Not including data for four co‐occurring RAS BRAF hotspot mutants.
a
Adjusting for mutational burden (all mutation types) in a logistic regression model with BRAF hotspot tumors as the reference group.
b
The pathway is more frequently mutated in the NF1 genomic subtype.
c
The pathway is more frequently mutated in the RAS hotspot genomic subtype.
d
The pathway is more frequently mutated in the RAS hotspot and triple‐wild‐type genomic subtypes.
e
The pathway is less frequently mutated in the triple‐wild‐type genomic subtype.