Multi-omics Analysis of Rare Brain Tumors Assists in Making More Informed Clinical Decisions

Our manuscript on rare embryonal brain tumors offers insights on 70 patients enrolled in multi-center clinical trials in the last 20 years. These tumors were initially thought to be a single entity, however, a multi-omics approach could segregate them into ten different entities. These entities have striking differences in their survival outcomes and also carry quite distinct molecular patterns.

Quite Distinct Entities

CNS: Central Nervous System

1. ETMR: embryonal tumor with multilayered rosettes
2. CNS_NB_FOXR2: CNS neuroblastoma with FOXR2 activation
3. HGG: high-grade glioma
4. CNS_SARC_CIC: CNS sarcoma with CIC rearrangement
5. HGNET_BCOR: high-grade neuroepithelial tumor with BCOR alteration
6. CNS_ET_NEC/NOS: CNS embryonal tumor not elsewhere defined/not otherwise specified
7. CNS_SARC_DICER: CNS sarcoma with DICER mutation
8. PXA: pleomorphic xanthoastrocytoma
9. EWS: Ewing’s Sarcoma
10. CPC: choroid plexus carcinoma

Entity-wise Survival Outcomes

The figure above shows how these two entities (CNS_NB_FOXR2 and ETMR) in our cohort have a significant difference in their survival outcomes. 80% of CNS_NB_FOXR2 patients survived five years after the diagnosis while only 20% of ETMR patients could make up to this mark.

Molecular Patterns

We have also described molecular patterns extracted from their RNAseq, Whole Exome Sequencing, and Methylation array data analysis. These data show a distinct molecular pattern associated with each of these entities (See Figure Below). For example, ETMR tumors have an extra copy of chromosome 2 and lost a copy of chromosome X, while HGNET_BCOR tumors have gene rearrangement in the BCOR gene and CNS_SARC_DICER have mutations in the DICER1 gene.

Interactive data portal

We also offer an interactive data portal to query these data and to answer a lot many questions beyond the analysis shown in this manuscript.

Manuscript

The manuscript is now published in the Acta Neuropathologica Journal. Check it out!

We hope the manuscript will broaden our understanding of these rare embryonal brain tumors with precise diagnosis and more informed clinical decisions.

Thanks to all the co-authors, patients, and families at St. Jude Children's Research Hospital