SPG20, a novel biomarker for early detection of colorectal cancer, encodes a regulator of cytokinesis

• Published in: Oncogene Vol. 30; no. 37; pp. 3967 - 3978
• Main Authors: Lind, G E, Raiborg, C, Danielsen, S A, Rognum, T O, Thiis-Evensen, E, Hoff, G, Nesbakken, A, Stenmark, H, Lothe, R A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-09-2011; Nature Publishing Group
• Subjects: 631/80/641/2090; 692/699/67/1504/1885; 692/699/67/1857; Adenoma; Apoptosis; Biological and medical sciences; Biological markers; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma - diagnosis; Carcinoma - genetics; Cell Biology; Cell cycle, cell proliferation; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Cytokinesis; Cytokinesis - genetics; Diagnosis; DNA damage; DNA Methylation; Down-Regulation; Feces; Feces - chemistry; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Human Genetics; Humans; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Molecular and cellular biology; Mortality; Mucosa; Oncology; Original; original-article; Physiological aspects; Promoter Regions, Genetic; Promoters; Proteins - genetics; Proteins - metabolism; Risk factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival; Tumorigenesis; Tumors; Norway; colorectal neoplasia; early detection; Spartin; cytokinesis; methylation; SPG20; Rectal disease; Cytodieresis; Colorectal cancer; Biological marker; Malignant tumor; Carcinogenesis; Colonic disease; Cell cycle; Digestive diseases; Intestinal disease; Early; Detection; Methylation; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2011.109

Colorectal cancer is a common disease with high mortality. Suitable biomarkers for detection of tumors at an early curable stage would significantly improve patient survival. Here, we show that the
SPG20
(spastic paraplegia-20) promoter, encoding the multifunctional Spartin protein, is hypermethylated in 89% of colorectal carcinomas, 78% of adenomas and only 1% of normal mucosa samples.
SPG20
methylation was also present in a pilot series of stool samples and corresponding tumors from colorectal cancer patients.
SPG20
promoter hypermethylation resulted in loss of mRNA expression in various cancer types and subsequent depletion of Spartin. We further showed that Spartin downregulation in cancer cells resulted in cytokinesis arrest, which was reversed when
SPG20
methylation was inhibited. The present study identifies
SPG20
promoter hypermethylation as a biomarker suitable for non-invasive detection of colorectal cancer, and a possible mechanism for cytokinesis arrest in colorectal tumorigenesis.