Mutation frequencies in adult vs pediatric T-ALL
| Gene . | Type of genetic aberration . | Frequency . | |
|---|---|---|---|
| Pediatric . | Adult . | ||
| NOTCH1 signaling pathway | |||
| FBXW7 | Inactivating mutations | 14 | 14 |
| NOTCH1 | Chromosomal rearrangements/activating mutations | 50 | 57 |
| Cell cycle | |||
| CDKN2A | 9p21 deletion | 61 | 55 |
| CDKN2B | 9p21 deletion | 58 | 46 |
| RB1 | Deletions | 12* | |
| Transcription factors | |||
| BCL11B | Inactivating mutations/deletions | 10 | 9 |
| ETV6 | Inactivating mutations/deletions | 8 | 14 |
| GATA3 | Inactivating mutations/deletions | 5 | 3 |
| HOXA (CALM-AF10, MLL-ENL and SET-NUP214) | Chromosomal rearrangements/inversions/expression | 5 | 8 |
| LEF1 | Inactivating mutations/deletions | 10 | 2 |
| LMO2 | Chromosomal rearrangements/deletions/expression | 13 | 21 |
| MYB | Chromosomal rearrangements/duplications | 7 | 17 |
| NKX2.1/NKX2.2 | Chromosomal rearrangements/expression | 8* | |
| RUNX1 | Inactivating mutations/deletions | 8 | 10 |
| TAL1 | Chromosomal rearrangements/5′ super-enhancer mutations/deletions/expression | 30 | 34 |
| TLX1 | Chromosomal rearrangements/deletions/expression | 8 | 20 |
| TLX3 | Chromosomal rearrangements/expression | 19 | 9 |
| WT1 | Inactivating mutation/deletion | 19 | 11 |
| Signaling | |||
| AKT | Activating mutations | 2 | 2 |
| DNM2 | Inactivating mutations | 13 | 13 |
| FLT3 | Activating mutations | 6 | 4 |
| JAK1 | Activating mutations | 5 | 7 |
| JAK3 | Activating mutations | 8 | 12 |
| IL7R | Activating mutations | 10 | 12 |
| NF1 | Deletions | 4 | 4 |
| KRAS | Activating mutations | 6 | 0 |
| NRAS | Activating mutations | 14 | 9 |
| NUP214-ABL1/ ABL1 gain | Chromosomal rearrangement/duplication | 8* | |
| PI3KCA | Activating mutations | 1 | 5 |
| PTEN | Inactivating mutations/deletion | 19 | 11 |
| PTPN2 | Inactivating mutations/deletion | 3 | 7 |
| STAT5B | Activating mutations | 6 | 6 |
| Epigenetic factors | |||
| DNMT3A | Inactivating mutations | 1 | 14 |
| EED | Inactivating mutations/deletions | 5 | 5 |
| EZH2 | Inactivating mutations/deletions | 12 | 12 |
| KDM6A/UTX | Inactivating mutations/deletions | 6 | 7 |
| PHF6 | Inactivating mutations/deletions | 19 | 30 |
| SUZ12 | Inactivating mutations/deletions | 11 | 5 |
| Translation and RNA stability | |||
| CNOT3 | Missense mutations | 3 | 8 |
| mTOR | Activating mutations | 5* | |
| RPL5 | Inactivating mutations | 2 | 2 |
| RPL10 | Missense mutations | 8 | 1 |
| RPL22 | Inactivating mutations/deletion | 4 | 0 |
| Gene . | Type of genetic aberration . | Frequency . | |
|---|---|---|---|
| Pediatric . | Adult . | ||
| NOTCH1 signaling pathway | |||
| FBXW7 | Inactivating mutations | 14 | 14 |
| NOTCH1 | Chromosomal rearrangements/activating mutations | 50 | 57 |
| Cell cycle | |||
| CDKN2A | 9p21 deletion | 61 | 55 |
| CDKN2B | 9p21 deletion | 58 | 46 |
| RB1 | Deletions | 12* | |
| Transcription factors | |||
| BCL11B | Inactivating mutations/deletions | 10 | 9 |
| ETV6 | Inactivating mutations/deletions | 8 | 14 |
| GATA3 | Inactivating mutations/deletions | 5 | 3 |
| HOXA (CALM-AF10, MLL-ENL and SET-NUP214) | Chromosomal rearrangements/inversions/expression | 5 | 8 |
| LEF1 | Inactivating mutations/deletions | 10 | 2 |
| LMO2 | Chromosomal rearrangements/deletions/expression | 13 | 21 |
| MYB | Chromosomal rearrangements/duplications | 7 | 17 |
| NKX2.1/NKX2.2 | Chromosomal rearrangements/expression | 8* | |
| RUNX1 | Inactivating mutations/deletions | 8 | 10 |
| TAL1 | Chromosomal rearrangements/5′ super-enhancer mutations/deletions/expression | 30 | 34 |
| TLX1 | Chromosomal rearrangements/deletions/expression | 8 | 20 |
| TLX3 | Chromosomal rearrangements/expression | 19 | 9 |
| WT1 | Inactivating mutation/deletion | 19 | 11 |
| Signaling | |||
| AKT | Activating mutations | 2 | 2 |
| DNM2 | Inactivating mutations | 13 | 13 |
| FLT3 | Activating mutations | 6 | 4 |
| JAK1 | Activating mutations | 5 | 7 |
| JAK3 | Activating mutations | 8 | 12 |
| IL7R | Activating mutations | 10 | 12 |
| NF1 | Deletions | 4 | 4 |
| KRAS | Activating mutations | 6 | 0 |
| NRAS | Activating mutations | 14 | 9 |
| NUP214-ABL1/ ABL1 gain | Chromosomal rearrangement/duplication | 8* | |
| PI3KCA | Activating mutations | 1 | 5 |
| PTEN | Inactivating mutations/deletion | 19 | 11 |
| PTPN2 | Inactivating mutations/deletion | 3 | 7 |
| STAT5B | Activating mutations | 6 | 6 |
| Epigenetic factors | |||
| DNMT3A | Inactivating mutations | 1 | 14 |
| EED | Inactivating mutations/deletions | 5 | 5 |
| EZH2 | Inactivating mutations/deletions | 12 | 12 |
| KDM6A/UTX | Inactivating mutations/deletions | 6 | 7 |
| PHF6 | Inactivating mutations/deletions | 19 | 30 |
| SUZ12 | Inactivating mutations/deletions | 11 | 5 |
| Translation and RNA stability | |||
| CNOT3 | Missense mutations | 3 | 8 |
| mTOR | Activating mutations | 5* | |
| RPL5 | Inactivating mutations | 2 | 2 |
| RPL10 | Missense mutations | 8 | 1 |
| RPL22 | Inactivating mutations/deletion | 4 | 0 |
Genes targeted by genetic alterations in >2% of T-ALL cases are shown. Calculation of the different frequencies is based on several previously published independent studies that analyzed pediatric and/or adult T-ALL patient cohorts. For frequency calculations, chromosomal rearrangements, copy-number variations and mutations were considered. For HOXA, TLX1, TLX3, TAL1, NKX2.1, NKX2.2, and LMO2, gene expression was also considered. The HOXA group includes cases that are positive for CALM-AF10, SET-NUP214, or MLL-ELN chromosomal rearrangements.
It was not possible to have separate numbers for pediatric and adult cases.