Table 1.
Clinical and molecular characteristics of H3-WT patients from ZERO.
| Patient ID | zcc120 | zcc183 | zcc316 | zcc339 | zcc446 |
|---|---|---|---|---|---|
| Age(years)/gender | 15/F | 3/M | 1/M | 8/M | 13/M |
| Histology | Glioblastoma | Anaplastic astrocytoma | Anaplastic astrocytoma | Glioblastoma | Anaplastic astrocytoma |
| Location | Thalamus, left | Thalamus, bilateral | Thalamus, left | Thalamus, right | Pons, left |
| IHC | H3K27M negative, loss of H3K27me3 nuclear staining, EZHIP positive | H3K27M negative, loss of H3K27me3 nuclear staining, EZHIP positive | H3K27M negative, loss of H3K27me3 nuclear staining, EZHIP N/A | H3K27M negative, loss of H3K27me3 nuclear staining, EZHIP positive | H3K27M negative, loss of H3K27me3 nuclear staining, EZHIP negative |
| Tumour purity (%) | 94 | 91 | 82 | 90 | 84 |
| Genetic alterations | NM_001105(ACVR1):c.983G > A (p.Gly328Glu); NM_006218(PIK3CA):c.1633G > A (p.Glu545Lys) | NM_005228(EGFR):c.2303_2311dupGCGTGGACA (p.Ser768_Asp770dup); NM_005378(MYCN):c.131C > T (p.Pro44Leu) | NM_005228(EGFR):c.2303_2311dupGCGTGGACA (p.Ser768_Asp770dup) | NM_001105(ACVR1):c.983G > T (p.Gly328Val); NM_006218(PIK3CA):c.1624G > A (p.Glu542Lys) | NM_000267(NF1):c.574C > T (p.Arg192Ter); NM_001126112(TP53):c.148_157delATTGAACAAT (p.Ile50GlyfsTer70) |
| Copy number alterations | 1p loss, 1q gain, chr2 gain, focal 14q gain/loss | 1q/19p co-polysomy | Chr3 gain | 1p loss, 1q gain, 15q loss | Focal 1p gain, 1q gain, chr2 gain, 3p loss, focal 4q gain, chr5 gain, focal 9q loss/gain, chr7 gain – includes EGFR (TPM 35.77, FC = 2.71), 8q gain, focal 9p biallelic loss, 10p gain, focal 11p loss, 11q gain, 12p gain and focal amp, 12q focal gain, 13q focal gains and losses, 16p gain, 17p loss |
| EZHIP expression (TPM) | 7.57 | 3.96 | 3.64 | 9.51 | 0.29 |
| DKFZ methylation classifier findings (v11b.4) | No match: methylation class diffuse midline glioma H3 K27M mutant (0.37) | No match: methylation class family glioblastoma, IDH wildtype (0.84) | No match | No match: methylation class family Glioblastoma, IDH wildtype (0.68) | No match: methylation class family glioblastoma, IDH wildtype (0.86) |
| DKFZ methylation classifier findings (v12.5) | No match: Medulloblastoma, SHH-activated, subclass 2 (novel) (0.43) | Match: diffuse midline glioma, H3 K27-altered, subtype EGFR-altered (0.99) | Match: diffuse midline glioma, H3 K27-altered, subtype EGFR-altered (0.99) | Match: diffuse midline glioma, H3 K27-altered, subtype H3 K27-mutant or EZHIP expressing (0.97) | No match: glioblastoma, IDH-wildtype (0.71) |
| No match: Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype (0.34) | No match: glioblastoma, IDH-wildtype, subtype posterior fossa (novel) (0.27) | ||||
| WHO 2021 diagnosis | Diffuse midline glioma, H3 K27-altered | Diffuse midline glioma, H3 K27-altered | Diffuse midline glioma, H3 K27-altered | Diffuse midline glioma, H3 K27-altered | Diffuse paediatric type high grade glioma, H3-wildtype and IDH-wildtype |
| Radiotherapy | Focal | Focal | Focal (30 Gy) | Focal (59.4 Gy) | Focal (59 Gy) |
| Chemotherapy | Temozolomide/lomustine | Dasatinib (as part of clinical trial) Temozolomide/lomustine | Carboplatin/etoposide/cyclophosphamide | Temozolomide; temozolomide/bevacizumab | Trametinib; ACT001; abemaciclib |
| Outcome | Died of disease | Died of disease | Alive with progressive disease | Alive with progressive disease | Died of disease |
| Follow-up (months) | 21 | 11 | 12 | 20 | 11 |
The five H3-WT midline gliomas with their corresponding zcc ID, age at diagnosis, gender (M-male, F-female), histology, location in the brain, IHC results, genetic alterations and copy number alterations as identified by WGS, EZHIP TPM expression as identified by RNA-seq, DKFZ methylation classification results, type of radiation and chemotherapy received, disease outcome, and time in month of last known follow-up.