Serum DNA Analysis: Potential Application for Diagnosis and Prognosis in Brain Cancer.
Genetic and epigenetic abrasions like loss of hetherozygosity and hypermethylation of gene
promoters are common aberration in gliomas. Detection of these aberrations serves as
diagnostic and prognostic tool. Examples: 1. oligodendrogliomas patients with combined
1p/19q LOH within the tumor respond better to chemotherapy and have better prognosis,
whereas LOH on chromosome 10q is a marker for worse prognosis. 2. GBM patients with
hypermethylation of the promoter of methyl-guanine-methyl-transferase (MGMT) in the tumor
respond better to alkylating agent and have better prognosis.
As sample materials for diagnosis should be easily accessible by a minimally invasive
procedure, there has been much interest in the potential use of nucleic acid markers in the
blood of patients with cancer.
It was demonstrated that LOH as well as hypermethylation could be detected in the
plasma/serum of patients with a variety of malignancies, suggesting that circulating
tumor-associated DNA in the blood of patients can be a key determinant in predicting genetic
and epigenetic abrasions in the tumor.
Objectives of the study:
Main objective: to find whether genetic abrasions in serum DNA represent the tumor DNA in
patients with brain tumor.
Is tumor DNA can be detected in the serum of only high grade tumors or also in low grade
Blood serum and tumor of patients are obtained anonymously, after the patient has signed a
consent form, prior to surgery as part of the procedure for tissue collection for the brain
tumor bank at Hadassah.
Part of the tumor is stained with hematoxylin-and-eosin and Histopathologic diagnosis is
performed by a pathologist.
DNA is extracted from whole blood, serum and tumor of all patients with low grade or high
In order to determine whether serum DNA represents the tumor DNA, LOH of 1p,19q,10q,17p,13q,
9p as well as methylation status of MGMT promoter will be tested in DNA samples from blood,
serum and tumor.
Observational Model: Defined Population, Primary Purpose: Screening, Time Perspective: Longitudinal, Time Perspective: Retrospective
TALI SIEGAL, MD
Hadassah Medical Organization
Israel: Israeli Health Ministry Pharmaceutical Administration