Promoter DNA methylation of oncostatin m receptor-beta as a novel diagnostic and therapeutic marker in colon cancer.
In addition to genetic changes, the occurrence of epigenetic alterations is associated with accumulation of both genetic and epigenetic events that promote the development and progression of human cancer. Previously, we reported a set of candidate genes that comprise part of the emerging "cancer methylome". In the present study, we first tested 23 candidate genes for promoter methylation in a small number of primary colon tumor tissues and controls. Based on these results, we then examined the methylation frequency of Oncostatin M receptor-beta (OSMR) in a larger number of tissue and stool DNA samples collected from colon cancer patients and controls. We found that OSMR was frequently methylated in primary colon cancer tissues (80%, 80/100), but not in normal tissues (4%, 4/100). Methylation of OSMR was also detected in stool DNA from colorectal cancer patients (38%, 26/69) (cut-off in TaqMan-MSP, 4). Detection of other methylated markers in stool DNA improved sensitivity with little effect on specificity. Promoter methylation mediated silencing of OSMR in cell lines, and CRC cells with low OSMR expression were resistant to growth inhibition by Oncostatin M. Our data provide a biologic rationale for silencing of OSMR in colon cancer progression and highlight a new therapeutic target in this disease. Moreover, detection and quantification of OSMR promoter methylation in fecal DNA is a highly specific diagnostic biomarker for CRC.
Kim
Myoung Sook
MS
Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
Louwagie
Joost
J
Carvalho
Beatriz
B
Terhaar Sive Droste
Jochim S
JS
Park
Hannah Lui
HL
Chae
Young Kwang
YK
Yamashita
Keishi
K
Liu
Junwei
J
Ostrow
Kimberly Laskie
KL
Ling
Shizhang
S
Guerrero-Preston
Rafael
R
Demokan
Semra
S
Yalniz
Zubeyde
Z
Dalay
Nejat
N
Meijer
Gerrit A
GA
Van Criekinge
Wim
W
Sidransky
David
D
D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D053681:Oncostatin M Receptor beta Subunit