We are developing an innovative, minimally invasive method to study the genetic spectrum of tumors metastatic and primary to the central nervous system (CNS). Cell free DNA (cfDNA) acts as a tumor fingerprint, allowing detection of genetic alterations that mark the variation and progression of disease. As a clinical tool, it may supplant the currently available and relatively insensitive methods of brain tumor diagnosis. As a scientific tool, novel tumor cfDNA mutations identified in CSF will allow for great insight into tumor biology, and more faithful animal modeling of these diseases.
Specific Aim 1 : Develop novel microfluidic chips to isolate and characterize cfDNA within the CSF of patients with primary and metastatic brain tumors.
Specific Aim 2 : Refine new sequencing techniques to characterize tumor cfDNA in CSF from patients with CNS tumors. Determine the feasibility of supplanting cytology with tumor cfDNA sequencing in the diagnosis of leptomeningeal metastasis.
Specific Aim 3 : Subtype primary brain tumors through the development of single-gene copy number variation sequencing of cfDNA in CSF. Summary: cfDNA in CSF from brain tumors shows great promise to track cancer's mutation profile, diagnose disease, and inform treatment. The techniques accelerated here may revolutionize the recognition of leptomeningeal metastases, and deepen our scientific understanding of brain tumor progression.

Public Health Relevance

Tumor cell free DNA (cfDNA) from cerebral spinal fluid (CSF) shows great promise to track the genetic mutation fingerprint of metastatic and primary brain tumors, transforming the diagnostic capacity and research insight into these difficult to treat neoplasms. Our proposed technology development seeks to revolutionize the recognition of leptomeningeal metastases, and deepen our understanding of how brain tumors progress. The access to and study of CSF, novel sequencing techniques for cfDNA, and the utilization of microfluidics make this an unique, collaborative, and translational project, ready to transition from proof of principle to versatile development of a dynamic clinical and research cancer tool.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA193046-03
Application #
9324707
Study Section
Special Emphasis Panel (ZCA1-TCRB-Q (J2))
Program Officer
Mckee, Tawnya C
Project Start
2015-06-12
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
3
Fiscal Year
2017
Total Cost
$199,823
Indirect Cost
$75,323
Name
Stanford University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Li, Yingmei; Pan, Wenying; Connolly, Ian D et al. (2016) Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases. J Neurooncol 128:93-100
Pan, Wenying; Gu, Wei; Nagpal, Seema et al. (2015) Brain tumor mutations detected in cerebral spinal fluid. Clin Chem 61:514-22