title: SPG20, a novel biomarker for early detection of colorectal cancer, encodes a regulator of cytokinesis.
abstract: 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.
authors.affiliation: Department of Cancer Prevention, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital, Oslo, Norway.
authors.forename: G E
authors.initials: GE
authors.lastname: Lind
authors.forename: C
authors.initials: C
authors.lastname: Raiborg
authors.forename: S A
authors.initials: SA
authors.lastname: Danielsen
authors.forename: T O
authors.initials: TO
authors.lastname: Rognum
authors.forename: E
authors.initials: E
authors.lastname: Thiis-Evensen
authors.forename: G
authors.initials: G
authors.lastname: Hoff
authors.forename: A
authors.initials: A
authors.lastname: Nesbakken
authors.forename: H
authors.initials: H
authors.lastname: Stenmark
authors.forename: R A
authors.initials: RA
authors.lastname: Lothe
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics; D048749:Cytokinesis / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D005243:Feces / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D011506:Proteins; C464787:SPART protein, human