Table 1 Clinical, pathologic, and molecular features of reported CNS tumors with CLIP2::MET fusion
Case 1 | Case 2 | Chowdhury et al. 2020 | Riedmeier et al. 2021 | Stucklin et al. 2021* | Stucklin et al. 2021* | |
|---|---|---|---|---|---|---|
Clinical data | ||||||
Age at the diagnosis | 4 yrs | 8 yrs | 30 yrs | 1 mo | <1 mo | 7 mo |
Sex | Male | Male | Female | Male | Female | Male |
Tumor location | Left occipital lobe | Right parieto-occipital lobe | Left parietal lobe | Left frontal/temporal lobe | Hemispheric, NOS | Hemispheric, NOS |
Diagnosis at presentation | GNT | GNT | GNT | HGG | IHG | IHG |
Treatment | GTR | GTR | GTR | Biopsy | Biopsy + Chemo | PR + Chemo |
Follow-up time | 0.5 yr | 3 yrs | 7 yrs | 5 mo | 0.7 yr | 0.5 yr |
Outcome | Alive | Alive | Alive | Alive | Alive | Alive |
Pathologic features (IHC) | ||||||
GFAP | Positive in subpopulation | Positive | Focal positivity | Focal positivity | n/a | n/a |
OLIG2 | Positive | Diffuse nuclear positivity | Focal positivity | n/a | n/a | n/a |
Synaptophysin | Granular positivity | Positive | Diffuse strong positivity | Negative | n/a | n/a |
NeuN | Negative in tumor cells | Positive in scattered tumor cells | Positive in tumor cells | n/a | n/a | n/a |
ATRX | Retained nuclear expression | Retained nuclear expression | Retained nuclear expression | Retained nuclear expression | n/a | n/a |
Ki-67 | Low index 1.07% | Low index 3% | Low index 0.4% | 20% | n/a | n/a |
H3K27me3 | Retained nuclear expression | Retained nuclear expression | n/a | n/a | n/a | n/a |
Molecular features | ||||||
Copy number alterations | Copy number losses involving 1p, 6p, 6q, 7q, 9p, 19q, and 22q | Gain of 1q, copy number alterations in 7q, and loss of 22q | Loss of 1p, gain of 1q, and copy number alterations in 7q | n/a | n/a | n/a |
Fusion exon pair by RNA-seq | CLIP2 exon 11::MET exon 15 | CLIP2 exon 11::MET exon 15 | CLIP2 exon 12::MET exon 15 | CLIP2::MET, exon number n/a | CLIP2 exon 12::MET exon 15 | CLIP2 exon 12::MET exon 15 |
MET expression by RNA-seq | Higher MET expression in exons 15-21, including the tyrosine kinase domain, than in exons 1-14 | Higher MET expression in exons 15-21, including the tyrosine kinase domain, than in exons 1-14 | n/a | n/a | n/a | n/a |
Methylation profiling | No match by RF, clustered with LGG, PA/GG ST in UMAP | No match by RF, clustered with LGG, DNT in UMAP | Clustered with LGG, DNT t-SNE map | Infantile hemispheric glioma | Infantile hemispheric glioma | Infantile hemispheric glioma |