Massachusetts Institute of Technology

The General Hospital Corporation

Dana-Farber-Cancer Institute Inc.

The Broad Institute, Inc.

Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts

Ruprecht-Karls-Universitat Heidelberg

Volker Hovestadt

Bradley Bernstein

Aviv Regev

J Christopher Love

Todd Michael Gierahn

Alexander K Shalek

Travis K Hughes

Andreas Von Deimling

Marc H Wadsworth, Ii

Itay Tirosh

Peter Van Galen

David Capper

Mario Suva

Ang A Tu

Mariella Filbin

David Jones

Martin Sill

Melanie Bewerunge-hudler

Stefan Pfister

The subject matter disclosed herein is generally directed to compositions and methods for treating diffuse gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-gliomas). Disclosed herein are gene signatures specific for tumor cell types and compositions for treatment of H3K27M gliomas. In one embodiment, PRC1 is targeted in a treatment regimen for H3K27M-gliomas.

Methods and compositions for targeting developmental and oncogenic programs in H3K27M gliomas

The present invention relates to methods of detecting region(s) of interest in a gene comprising a polyA tail. The region(s) of interest can include gene(s), region(s), mutation(s), deletion(s), insertion(s), indel(s), and/or translocation(s). The region(s) can be greater than or less than 1 kilobases from the polyA tail. Methods can include forming a library of single cell transcripts comprising the region(s) in close proximity to a cell barcode and a unique molecular identifier (UMI). Methods for distinguishing cells by genotype can include amplifying the transcripts using PCR methods and detecting the cell barcode and UMI using single cell sequencing methods. Transcripts can be enriched using tagged region-specific PCR primers. Cell barcodes can be brought into close proximity to the region(s) by circularizing the transcripts. Sequencing of the transcripts can include using primer binding sites added during PCR amplification and library indexes for multiplexed sequencing.

Single cell sequencing libraries of genomic transcript regions of interest in proximity to barcodes, and genotyping of said libraries

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Boston, MA, United States of America

Volker Hovestadt