Methylation markers for small cell lung cancer in peripheral blood leukocyte DNA.
BACKGROUND
Small cell lung cancer (SCLC) is the most aggressive form of lung malignancy.


METHODS
To identify and validate potential DNA methylation markers for risk assessment and disease detection, we examined peripheral blood leukocyte DNA specimens for methylation differences between SCLC cases and controls. We tested 1505 CpG sites using the Illumina Beadchip assay and validated 9 CpG sites using pyrosequencing technology.


RESULTS
In 44 matched SCLC case-control pairs, we identified significant differences at 62 CpG sites (false discovery rate < or =0.05) in 52 independent genes. Of those, we further determined 43 sites in 36 genes with a mean methylation level difference greater than 0.03 between the cases and controls. We then selected and validated 9 CpG sites for methylation differences in an independent set of 138 matched case-control pairs. The 9 validated CpG sites predicted a higher risk for cases than controls in 85.8% of all pairs of cases and controls, and 2 (in genes CSF3R and ERCC1) jointly contributed most of the discriminating ability.


CONCLUSIONS
Our replicated results demonstrated feasibility of applying large-scale methylation arrays for biomarker discovery and subsequent validation in peripheral blood DNA. The CpG sites identified in this study may potentially assist in risk prediction and diagnosis of SCLC.
Wang
Liang
L
Department of Laboratory Medicine and Pathology, Mayo Clinic, College of Medicine, Rochester, Minnesota 55905, USA.
Aakre
Jeremiah A
JA
Jiang
Ruoxiang
R
Marks
Randolph S
RS
Wu
Yanhong
Y
Chen
Jun
J
Thibodeau
Stephen N
SN
Pankratz
V Shane
VS
Yang
Ping
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000097:blood / Q000209:etiology / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged
D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases