Table 2.
Catalog of genes targeted by recurrent molecular genetic abnormalities in adult AMLs as detected by NGS technologies.
| Gene symbol | Gene name | Identified by | Leukemia type | Frequency (%) | Detailed leukemia subtypes (%)a | Mutation type/s | Status | Reference |
|---|---|---|---|---|---|---|---|---|
| DNMT3A | DNA (cytosine-5-)-methyltransferase-3-alpha | Whole-genome | H-M1/NK | 62/281 (22.0)b | M0 (10), M1 (25.4), M2 (16.7), M3 (0), M4 (32.8), M5 (57.1), M6 (0), M7 (33.3) | Non-synonymous SNV | Novelc | Ley et al. (2010) |
| Whole-genome | H-M1/NK | 11/38 (28.9)d | Not shown | Non-synonymous SNV | Novel | Ley et al. (2010) | ||
| Exome capture | H-NK | 32/355 (9.0) | M1 (0), M2 (0), M3 (0), M4 (13.6), M5 (20.5) | Non-synonymous SNV | Novel | Yan et al. (2011) | ||
| Exome capture | H-NK(*) | 34/195 (17.4) | – | Non-synonymous SNV | Novel | Grossmann et al. (2011) | ||
| Whole-genome | H-NK | 49/200 (24.5) | Not shown | Non-synonymous SNV, frame-shift indel | Novel | Ding et al. (2012) | ||
| FLT3 | Fms-related tyrosine kinase 3 | Exome capture | H-NK | 21/112 (18.8) | M5 | Non-synonymous SNV, ITD | Known | Yan et al. (2011) |
| Whole-genome | H-M1/NK | 51/185 (27.6) | Not shown | ITD | Known | Ley et al. (2008) | ||
| Whole-genome | H-NK | 52/200 (26.0) | Not shown | Non-synonymous SNV, ITD | Known | Ding et al. (2012) | ||
| IDH1 | Isocitrate dehydrogenase 1 (NADP+), soluble | Whole-genome | H-M1/NK | 16/188 (8.5) | Not shown | Non-synonymous SNV | Novel | Mardis et al. (2009) |
| Whole-genome | H-NK | 20/200 (10.0) | Not shown | Non-synonymous SNV | Novel | Ding et al. (2012) | ||
| IDH2 | Isocitrate dehydrogenase 2 (NADP+), mitochondrial | Whole-genome | H-NK | 19/200 (9.5) | Not shown | Non-synonymous SNV | Novel | Ding et al. (2012) |
| MLL | Myeloid/lymphoid or mixed-lineage leukemia | Exome capture | H-NK | 22/112 (19.6) | M5 | Translocation or partial tandem duplication | Known | Yan et al. (2011) |
| NPM1 | Nucleophosmin (nucleolar phosphoprotein B23, numatrin) | Whole-genome | H-M1/NK | 43/180 (23.9) | – | Frame-shift indel | Known | Ley et al. (2008) |
| Whole-genome | H-M1/NK | Not validated | – | Frame-shift indel | Known | Mardis et al. (2009) | ||
| Whole-genome | H-NK | 53/200 (26.5) | Not shown | Frame-shift indel | Known | Ding et al. (2012) | ||
| NRAS | Neuroblastoma RAS viral (v-ras) oncogene homolog | Whole-genome | H-M1/NK | 20/188 (10.6) | Not shown | Non-synonymous SNV | Known | Mardis et al. (2009) |
| Exome capture | H-NK | 12/112 (10.7) | M5 | SNV | Known | Yan et al. (2011) | ||
| RUNX1 | Runt-related transcription factor 1 | RNA-seq | H-M1/NK | 9/95 (9.5) | Not shown | Non-synonymous SNV | Known | Greif et al. (2011b) |
| Exome capture | H-NK | Not validated | M5 | Frame-shift indel | Known | Yan et al. (2011) | ||
| Whole-genome | H-NK | 17/200 (8.5) | Not shown | Non-synonymous SNV, frame-shift indel | Known | Ding et al. (2012) | ||
| TTN | Titin | Whole-genome | H-NK | 13/200 (6.5) | Not shown | In-frame indel, Non-synonymous SNV | Novel | Ding et al. (2012) |
| WT1 | Wilms tumor 1 | Exome capture | H-NK | 3/112 (2.7) | M5 | Frame-shift indel, in-frame indel | Known | Yan et al. (2011) |
| Whole-genome | H-NK | 13/200 (6.5) | Not shown | Frame-shift indel | Known | Ding et al. (2012) |
The 10 genes listed in this table were found in at least 5% of the tumor samples. SNV, single nucleotide variant; H, human, M, mouse; NK, normal karyotype; asomatic mutations checked only in the same leukemia subtypes where originally identified; bvalidation performed by Sanger re-sequencing of DNMT3A exons in 281 samples; cidentified through array-based genomic re-sequencing also by Yamashita few months earlier Yamashita et al. (2010); dvalidation performed in 38 samples by whole-genome sequencing; NK(*) are normal karyotype AML patients not showing NPM1, CEBPA, FLT3–ITD, or MLL–PTD mutations.