TABLE 1.
Molecular, phenotypic, and clinical features of different cancer-associated SF3B1 mutations
| Residues found in the SF3B1 hotspot mutational pocket | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| SF3B1 mutation | E592K | E622D | R625H | H662Q | K666R | K666N | K700E | K741N | G742D | E902K |
| HEAT repeat | 2 | 3 | 3 | 4 | 4 | 4 | 5 | 6 | 6 | 11 |
| Molecular association with SUGP1 | ||||||||||
| AF-M-predicted direct interaction with SUGP1 | ✗ | ✗ | ✗ | ✓ | ✗ | ✗ | ✓ | ✓ | ✗ | ✗ |
| AF-M-predicted proximity to mutational pocket | ✗ | ✓ | ✓ | — | ✓ | ✓ | — | — | ✓ | ✗ |
| Experimentally validated to disrupt SF3B1–SUGP1 interaction | ✗ | ✓ | ✓ | ✓ | N/A | +/− | ✓ | N/A | N/A | N/A |
| RNA missplicing of MDSRS-related transcripts | ||||||||||
| MAP3K7 | ✗ | ✓ | ✓ | N/A | ✓ | +/− | ✓ | ✓ | ✓ | ✗ |
| TMEM14C | ✗ | ✓ | ✓ | N/A | + +/− | +/− | ✓ | N/A | ✓ | N/A |
| ABCB7 | ✗ | ✓ | N/A | ✓ | +/− − | +/− | ✓ | N/A | ✓ | N/A |
| Clinical and pathological features | ||||||||||
| Disease/Frequency | sAML (2.5%) | N/A | UVM (15%) MDS | MDS CLL | MDS-RS (18%) sAML (18%) CLL | MDS-RS (1.5%) sAML (28%) CLL | MDS (30%) MDS-RS (86%) CLL/sAML/ PDAC/BRCA | CLL (13%) MDS (rare) | CLL (19%) MDS (rare) | BLAC (16%) |
| Co-occurring mutations | RUNX1 | TET2 DNMT3A | TET2 DNMT3A | TET2 DNMT3A | TET2 JAK2 | FLT3 NPM1 JAK2 | DNMT3A ASXL1 TET2 | N/A | TET2 | N/A |
| Prognostic significance | ✗ | N/A | N/A | — | N/A | ✗ | ✓ | V | ✗ | N/A |
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References for each mutation are mentioned throughout the text. (N/A) Nonavailable, (MDS) myelodysplastic syndromes, (MDS-RS) MDS with ring sideroblasts, (sAML) secondary acute myeloid leukemia, (CLL) chronic lymphocytic leukemia, (UVM) uveal melanoma, (PDAC) pancreatic ductal adenocarcinoma, (BLAC) bladder urothelial carcinoma, (BRCA) breast adenocarcinoma.
