Table 1.
Significantly and recurrently mutated genes in T-ALL
| Gene | Number of subjects with mutations |
Gene function | Associated age group |
Associated pathologies with genomic alterations |
|---|---|---|---|---|
| NOTCH1 | 29/67 (43.3%)a | Transmembrane receptor, releases intracellular NOTCH1 transcriptional enhancer upon activation | None | T-ALL25, CLL26,27, lung cancer28, head and neck cancer29,30, breast cancer31,32 |
| FBXW7 | 8/67 (11.9%) | Part of ubiquitin ligase complex targeting cyclin E, MYC and NOTCH1 | None | T-ALL33, various cancer types34 |
| WT1 | 7/67 (10.4%) | Zinc-finger transcription factor | None | T-ALL35, AML36, Wilms tumor |
| BCL11B | 5/67 (7.5%) | Zinc-finger transcription factor | None | T-ALL37 |
| CNOT3 | 8/211 (3.8%) | Part of the CCR4-NOT complex that regulates gene expression | Adult | |
| RPL10 | 11/211 (5.2%) | Ribosomal protein of the 60S ribosomal subunit | Pediatric | Autism38,39 |
| RPL5 | 4/211 (1.9%) | Ribosomal protein of the 60S ribosomal subunit | None | Diamond Blackfan anemia11 |
| JAK3 | 7/67 (10.4%) | Kinase involved in cytokine receptor signaling | None | T-ALL8,40, various myeloid and lymphoid malignancies |
| PTEN | 4/67 (6.0%) | Phosphatase antagonizing PI3K function | None | T-ALL18, various cancer types |
| DNM2 | 4/67 (6.0%) | Microtubule-associated GTPase | None | T-ALL8, Charcot-Marie-Tooth disease41, centronuclear myopathy41 |
| ODZ2 | 2/67 (3.0%) | May function as a cellular signal transducer | None | |
| PHF6 | 12/67 (17.9%) | Plant homeodomain-like finger (PHF) family protein that may regulate transcription | Adult | T-ALL42, AML43, Borjeson-Forssman-Lehmann syndrome44 |
| TET1 | 4/67 (6.0%) | Epigenetic regulator converting methylcytosine (5mC) to 5-hydroxymethylcytosine (5-hmC) | None | t(10;11)(q22;23) (MLL-TET1 fusion) in AML and B-ALL45–47 |
| KDM6A | 3/67 (4.5%) | Histone demethylase for Lys27 of histone H3 | None | Various cancer types48,49, Kabuki syndrome50 |
| MAGEC3 | 2/67 (3.0%) | Gene function unknown, only expressed in normal testis and in various tumor types | None | Diffuse large B-cell lymphoma51 |
CLL, chronic lymphocytic leukemia; AML, acute myeloid leukemia; B-ALL, B-cell acute lymphoblastic leukemia.
a
Mutations in NOTCH1 were hard to identify by exome sequencing due to poor capture efficiency and resulting low sequence coverage of NOTCH1. The reported mutation number reflects NOTCH1 mutations detected by complementary Sanger sequencing.