Identification of New Diagnostic Biomarkers for Intracranial Germ Cell Tumors
Abstract
This proposal outlines a 3-year career development award for Dr. Joanna Gell, M.D., a pediatric hematologist-oncologist pursuing an academic career as a physician-scientist. The proposal is designed to help her develop into an independent scientific researcher focusing on basic and translational germ cell tumor (GCT) biology. GCTs are a unique group of tumors primarily affecting adolescents and young adults. GCTs are complex, as they encompass multiple subtypes and arise in multiple locations, including intracranial locations. Intracranial GCTs (iGCTs) primarily arise in deep brain locations, the pituitary and pineal glands. iGCTs often pose a diagnostic and therapeutic conundrum due to limitations in obtaining safe and adequate tumor biopsies for diagnosis and subtype assignment. However, appropriate diagnosis of iGCT subtypes is critically important, as it has both prognostic and therapeutic consequences. Given that surgical biopsies pose a danger to iGCT patients, these patients are ideal candidates for the use of liquid biopsies through the minimally invasive means of cerebrospinal fluid (CSF) sampling. Currently, there are two protein biomarkers that are measured in the blood or CSF of patients suspected to have iGCTs, to aid in diagnosis and monitor disease. However, these two proteins have limitations, including not specific to iGCTs and being presented in a small fraction of iGCT patients. The goal of this project is to identify new diagnostic and potential therapeutic biomarkers for iGCTs by evaluating bio-banked CSF samples from patients with iGCTs. I propose that we can identify genetic and epigenetic signatures that are specific to iGCTs, in the CSF, in order to avoid tissue biopsy. The project s long-term objective is to improve immediate and long-term outcomes for iGCTs patients by making the correct diagnosis and correct subtype assignment. Aim 1 seeks to use a special type of RNA, called microRNA. Many cancers have a unique microRNA signature. I will profile bio-banked CSF for a specific microRNA signature to diagnose and sub-classify iGCTs. Aim 2 will use a unique type of DNA that is shed into surrounding fluid from tumors, called circulating tumor DNA (ctDNA). I will use bio-banked CSF to extract ctDNA and identify tumor mutations and DNA methylation patterns that are found in iGCTs, to aid in diagnosis and classification. Results of this project have the potential to substantially impact the way we diagnose patients with iGCTs and subsequently assign current treatment regimens and/or new therapeutics. Identification of new biomarkers has the potential not only to improve diagnosis but also to monitor disease response and recurrence. The training that I will receive in this project, through laboratory-based techniques, will provide the solid translational-biology and cancer-biology skills needed to fulfill my long-term career goals, as an academic expert in germ cell tumor. My career guide, Dr. Ching Lau, M.D., Ph.D., has a proven record in iGCT research, as well as a strong record in mentoring junior faculty to independence. The guidance that I will have from my career guide, Dr. Ching Lau, as well as other advisors and collaborators, will be fundamental for preparing me for a career as an independent investigator in germ cell tumors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210177
Entities
People
- Joanna Gell
Organizations
- Jackson Laboratory
- United States Army