Cracking the Histone Code: Characterizing Pediatric Brain Tumor Epigenetics using Cerebrospinal Fluid

Email Principal Investigator
Ongoing
Specimen
HGG
Glioma
Default project image
saratsisamanda_epi.jpg

Amanda Muhs Saratsis

Ann & Robert H. Lurie Children’s Hospital of Chicago
Chicago, Illinois, USA

CBTN Samples Used

4

CBTN Participants

6

CBTN Samples

Backer

Northwestern University Clinical and Translational Sciences Institute (NUCATS)

The Ann & Robert H. Lurie Faculty Practice Plan

The Frankel Foundation

The Pediatric Cancer Research Foundation

About this

Project

The goal of this project is to determine patterns of tumor-specific protein expression in tumor tissue and cerebrospinal fluid (CSF) collected from children with glioma and normal controls using novel proteomics techniques. Expression patterns of specific proteins known as Histones will be correlated with patterns of gene expression (RNA-Seq) that contribute to tumor formation in order to determine their utility as clinical biomarkers of disease and response to therapy.

Ask The

Scientists

Ask the scientists

What are the goals of this project?

The goal of this project is identify isoforms of Histone proteins that contribute to tumor formation and reflect treatment response.

What is the impact of this project?

We hypothesize that these tumor epigenetic signatures may not only serve as clinically accessible biomarkers of disease for diagnosis and molecular characterization, but will also provide insight to the mechanism of tumor formation for improved treatment. Specifically, identified epigenetic signatures will implicate activity of specific histone modifying enzymes that alter chromatin structure and function to result in tumorigeneic gene expression patterns, revealing candidate genes and histone modifying enzymes for testing as potential therapeutic targets in future research. This research therefore has the potential to improve clinical outcomes for children with glioma by facilitating safer clinical diagnosis, informing stratification to specific and more effective therapeutic agents, and enabling monitoring of treatment response, all by using clinically accessible CSF specimens in lieu of tumor tissue.

Why the CBTN request is important to this project?

Matched CSF and tumor tissue specimens are required to conduct the proposed research. The CBTN contains this precious resource from children with low grade, high grade and diffuse intrinsic pontine glioma, with multiple collection events in some instances. In addition, the CBTN is in the process of acquiring whole exome and transcriptome (RNA-Seq) data on a large cohort of their banked glioma specimens. We are requesting paired CSF and fresh glioma tumor tissue for proteomics and ChIP-Seq, and will integrate these results with Nantomics RNA-Seq data (where available) for these specimens.

Specimen Data

The Children's Brain Tumor Network contributed to this project by providing cerebral spinal fluid and tissue samples.