Serum DNA as a tool for cancer patient management.
OBJECTIVE
Genetic analysis has shown that cell-free circulating DNA in plasma or serum of cancer patients shares similar genetic alterations to those described in the corresponding tumor. One of the most important alterations involved in carcinogenesis is aberrant promoter methylation. The interest in this field has grown due to the implementation of the methylation-specific PCR (MSP) assay. The main objective of this study is to analyze the methylation status of different genes in tumor and serum DNA obtained at the time of surgery in two different tumor models (glioblastoma [GBM] and non-small-cell lung cancer [NSCLC]) and their relationship to clinico-pathological characteristics and response to chemotherapy.


METHODS
Using MSP assay, we assessed the methylation status of MGMT, RASSF1A, p16, DAPK, TMS-1 in tumor and serum DNA obtained at time of surgery or stereotactic biopsy from 28 GBM patients and from 51 NSCLC patients.


RESULTS
In GBM patients, the prevalence of MGMT, p16, DAPK, and RASSF1A promoter methylation was 38.1%, 66.7%, 52.4%, 57.1%, respectively, in glioma tissue, and 39.3%, 53.6%, 34.3%, 50%, respectively, in serum. A high correlation between methylation in tumor and serum (Spearman test p = 0.0001) was observed. In NSCLC patients, RASSF1A, DAPK and TMS-1 were methylated in 34%, 45% and 35% tumors, respectively, and in 34%, 40% and 34% serum, respectively. A good correlation was found between alterations found in tumor and serum (Spearman test p = 0.0001).


CONCLUSIONS
The study of serum or plasma DNA has opened new roads for translational research and new strategies for molecular diagnosis. Due to the similarities of alterations found in serum DNA and primary tumor, we can use this tool to calculate the risk of local or distant recurrence and its relationship with survival and its value in patient follow-up to evaluate response to therapy.
Ramirez
J L
JL
Medical Oncology Service, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Ctra Canyet, s/n, 08916 Badalona, Barcelona, Spain.
Taron
M
M
Balaña
C
C
Sarries
C
C
Mendez
P
P
de Aguirre
I
I
Nuñez
L
L
Roig
B
B
Queralt
C
C
Botia
M
M
Rosell
R
R
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D004247:DNA