Figure 1: Pedigree of described kindred and summary of molecular
results
Individuals with malignant CNS tumors and leukemia are highlighted inA. The index patient is marked by an oblique arrow. ConfirmedSMARCB1 exon 6 gain carriers (gain+) and non-carriers (gain-) are
identified. Carriers III.2 and III.4 are unaffected at
age 38 and 33 years. Specimens from individual IV.1 were not
available. Molecular results from available samples are summarized inB . MLPA, multiplex ligation-dependent probe amplification;t -SNE, t -distributed stochastic neighbour embedding
Figure 2: Analysis of CNS tumors from II.2 and III.1
Both ATRT (A,C ) and ependymoma (B,E ) display typical
histology with rhabdoid features (C ) or Astra-positive matrix,
respectively, (E ) as hallmark features. Both tumors were
negative for SMARCB1 by immunohistochemistry (D, F ) with arrows
indicating non-neoplastic ependymal cells as an internal positive
control. Analysis of the DNA methylation profiles revealed a classifier
score of 0.48 for the ATRT (0.38 for the TYR-subclass, not shown) and a
score < 0.3 for the ependymoma (not shown). Using t -SNE
together with > 2500 cases from 82 brain tumor classes from
Capper et al.1, the ATRT clustered with the Tyrosinase
subclass (zoom-in shown in G ) and the ependymoma with the
myxopapillary subclass (zoom-in shown in I ). Copy number plots
are shown in (H ) and (J ). Scale bar in Acorresponds to 100 µm in A, B . Scale bar in C corresponds to 10
µm in C-F .