Table 1.
Summary of the literature review of adult cases of H3K27M-mutant diffuse midline gliomas.
| Author, Year | Meyronet, 2017 | Solomon, 2016 | Ebrahimi, 2019 | Schreck, 2019 | Wang, 2018 |
Kleinschmidt, 2018 | Jiang, 2019 | Enomoto, 2020 |
Aihara, 2013a | Yikui, 2019a | Daoud, 2018a | He, 2019 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adult H3 K27 M gliomas, n | ||||||||||||
| H3F3A K27M | 20 | NR | 28 | 18 | 35 | 13 | 57 | 11 | 10 | 10 | 7 | 1 |
| HIST1H3B K27M | 1 | NR | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total | 21 | 20 | 29 | 18 | 35 | 13 | 57 | 11 | 10 | 10 | 7 | 1 |
| Age at diagnosis, years | ||||||||||||
| Median | 32 | NR | 37 | 38 | NR | 52 | 35 | NR | 38 | 32 | 41 | |
| Range | 18–82 | NR | 18-73 | 30-68 | NR | 2-81 | NR | NR | 17-46 | 18-54 | 25-54 | |
| Sex | ||||||||||||
| Male | 9/21 | NR | 19/29 | 8/18 | 19/35 | 4/13 | 34/57 | NR | NR | 6/10 | 6 | |
| Female | 12/21 | NR | 10/29 | 10/18 | 16/35 | 9/13 | 23/57 | NR | NR | 4/10 | 1 | |
| Clinical presentation | ||||||||||||
| Intracranial hypertension | 6/21 | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | 1 |
| Ataxia | 5/21 | |||||||||||
| Cranial Nerve Palsy | 4/21 | |||||||||||
| Sensorimotor deficits | 7/21 | |||||||||||
| Location, nb | ||||||||||||
| Midline cortex | 0 | NR | 0 | 0 | NR | 0 | 0 | NR | ||||
| Corpus Callosum | 0 | 0 | 1/18 | NR | 0 | 0 | ||||||
| Spinal cord | 6/21 | NR | 6/29 | 2/18 | 10/35 | 4/13 | 3/57 | NR | ||||
| Thalamus | 5/21 | NR | 15/29 | 3/18 | 7/35 | 7/13 | 33/57 | NR | 10 | 10 | ||
| Brainstem | ||||||||||||
| Midbrain | 1/21 | NR | NR | 2/18 | NR | 0 | NR | NR | 2/7 | |||
| Pons | 1/21 | NR | NR | 4/18 | NR | 1/13 | NR | NR | 2/7 | |||
| Floor of 4th Ventricle | 1/21 | NR | NR | 0 | NR | 0 | NR | NR | 2/7 | |||
| Medulla | 2/21 | NR | NR | 0 | NR | 0 | NR | NR | 1/7 | |||
| Total brainstem | 5/21 | NR | 7/29 | 6/18 | 11/35 | 1/13 | 15/57 | NR | 7 | |||
| Cerebellum | 3/21 | NR | 1/29 | 6/18 | NR | 0 | NR | |||||
| Hypothalamus | 1/21 | NR | 1/29 | 0 | NR | 1/13 | 1/57 | NR | 1 | |||
| Pineal region | 1/21 | NR | 0 | 0 | NR | 0 | 5/57 | NR | ||||
| Basal ganglia | 0 | NR | 2/29 | 0 | NR | 0 | 0 | NR | ||||
| 3rd Ventricle | 0 | NR | 2/29 | 0 | NR | 0 | 0 | NR | ||||
| Leptomeningeal involvement | 1/18 | NR | 0/29 | NR | NR | 1/13 | NR | NR | NR | NR | NR | 0 |
| Contrast Enhancement | 9/18 | NR | NR | 15/18 | NR | NR | 46/57 | NR | NR | NR | 1/6 | 1 |
| WHO 2007 Grade | ||||||||||||
| Grade I Grade II |
03/21 | NRNR | 1/296/29 | 00 | NRNR | 1/131/13 | NRNR | NRNR | 00 | NR NR |
NR NR |
|
| Grade III | 0 | NR | 8/29 | 6/18 | NR | 7/13 | NR | NR | 4/10 | NR | NR | |
| Grade IV | 11/21 | NR | 14/29 | 11/18 | NR | 5/13 | NR | NR | 5/10 | NR | NR | |
| Uncertain | 7/21 | NR | 0 | 1/18 | NR | 0 | NR | NR | 0 | NR | NR | |
| Molecular Characteristics | ||||||||||||
| IDH mutation | 0 | NR | 0 | 0 | 0 | NR | 0 | NR | 0 | 0 | 0 | 0 |
| MGMT promotor | 1/21 | NR | 0 | 1/5 | NR | NR | 0 | NR | 1/7 | ∼17% | NR | NR |
| methylation | 0 | NR | NR | NR | NR | 1/9 | NR | NR | 0 | NR | NR | NR |
| EGFR amplification | 0 | NR | 0 | 0 | NR | NR | NR | NR | NR | NR | 0 | NR |
| BRAF V600E mutation | 2/19 | NR | NR | NR | NR | NR | 1/27 | NR | NR | 0 | NR | NR |
| TERT promotor | NR | NR | 11/29 | 1/12 | 8/35 | 4/7 | NR | NR | 2/7 | NR | 0 | 1 |
| mutation | NR | NR | 0 | NR | NR | NR | NR | NR | NR | NR | NR | 0 |
| ATRX mutation | 11/21 | NR | 3/5 | NR | 26/35 | NR | NR | NR | 2/7 | ∼58% | 1/6 | 1 |
| ACVR1 | 21/21 | NR | NR | NR | 34/34 | NR | NR | NR | NR | ∼17% | NR | 1 |
| TP53 | NR | NR | NR | NR | NR | 3/7 | NR | NR | NR | NR | NR | NR |
| Olig 2 expression | NR | NR | NR | NR | NR | NR | 0 | NR | NR | NR | NR | NR |
| PTEN Loss | NR | NR | NR | NR | NR | NR | NR | NR | 3/7 | NR | NR | NR |
| 1p/19q Codeletion | NR | NR | NR | NR | NR | NR | NR | NR | 1/7 | NR | NR | NR |
| NF1 | NR | NR | NR | NR | NR | NR | NR | NR | 1/7 | NR | NR | NR |
| CREBBP | ||||||||||||
| FGFR1 | ||||||||||||
| Extent of resection | ||||||||||||
| GTR | 0 | NR | NR | 1/18 | NR | NR | 15/57 | NR | 1/10 | 1/10 | NR | 1 |
| STR | 5/21 | NR | NR | 4/18 | NR | NR | 23/57 | NR | 1/10 | 5/10 | NR | |
| PR/ Biopsy | 16/21 | NR | NR | 12/18 | NR | NR | 18/57 | NR | 8/10 | 4/10 | 2/7 | |
| Unknown | 0 | NR | NR | 1/18 | NR | NR | 0 | NR | 0/10 | 0/10 | 2/7 | |
| Treatment | ||||||||||||
| Surgery + RT + CT | 12/21 | NR | NR | 11/18 | NR | NR | 28/57 | NR | 10/10 | 10/10 | 2/7 | 1 |
| Surgery + RT | 2/21 | NR | NR | 0 | NR | NR | 9/57 | NR | 0 | 0 | 0 | |
| Surgery + CT | 3/21 | NR | NR | 0 | NR | NR | 5/57 | NR | 0 | 0 | 0 | |
| Surgery alone | 3/21 | NR | NR | 0 | NR | NR | 15/57 | NR | 0 | 0 | 1/7 | |
| RT alone | 0 | NR | NR | 0 | NR | NR | 0 | NR | 0 | 0 | 0 | |
| CT alone | 4/21 | NR | NR | 0 | NR | NR | 0 | NR | 0 | 0 | 0 | |
| CT + RT | 0 | NR | NR | 0 | NR | NR | 0 | NR | 0 | 0 | 2/7 | |
| Observation/Palliation | 3/21 | NR | NR | 6/18 | NR | NR | 0 | NR | 0 | 0 | 0 | |
| Unknown | 0 | NR | NR | 1/18 | NR | NR | 0 | NR | 0 | 0 | 2/7 | |
| Post-operative complications | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | ||
| Cranial nerve palsy | 21/57 | |||||||||||
| Motor deficit | 11/57 | |||||||||||
| Sensory deficit | 0 | 1 | ||||||||||
| Ataxia | 15/57 | |||||||||||
| Median OS, months | 19.6 | NR | 16.1 | 17.6 | NR | 8.4 | 16 | 17 | 10.4 | 7 | 9 | 9 |
Abbreviations: ACVR1, activin A receptor type 1; ATRX, α thalassemia/mental retardation syndrome X-linked; CT, chemotherapy; CREBBP, CREB binding protein; EGFR, epidermal growth factor receptor; FGFR1, fibroblast growth factor receptor 1; GTR, gross total resection; IDH, isocitrate dehydrogenase; MGMT, O(6)-Methylguanine-DNA methyltransferase; NF1, Neurofibromin 1; NR, not reported; Olig 2, Oligodendrocyte transcription factor 2; PR, partial resection; OS, overall survival; PTEN, phosphatase and tensin homolog; RT, radiotherapy; STR, subtotal resection; TERT, telomerase reverse transcriptase; TP53, tumor protein 53.
These series described cases exclusively arising in the brainstem (Daoud) or thalamus (Aihara, Yikui).
Totals may exceed 100% because some lesions involve more than one anatomic location.