title: The recently suggested intestinal cancer stem cell marker DCLK1 is an epigenetic biomarker for colorectal cancer.
abstract: Recently, Dclk1 expression was identified to be an intestinal cancer stem cell specific biomarker in mouse models, implicating a potential role for targeting the DCLK1-postive cancer cells as a treatment for colorectal cancer. Using quantitative methylation specific PCR (qMSP) we here demonstrated that the DCLK1 promoter is hypermethylated in the vast majority of colorectal cancers (134/164; 82%), with no methylation in the normal mucosa samples (0/106). We further showed by Affymetrix exon arrays that DCLK1 is significantly downregulated in human colorectal cancer (n = 125) compared with normal colonic mucosa (n = 15), which was further confirmed by real-time RT-PCR of a subgroup of the samples. Additionally, a significant negative correlation was observed between methylation and DCLK1 expression in 74 cancer cell lines derived from 15 different tissues, and gene expression increased significantly after epigenetic drug treatment of initially methylated cancer cell lines. These findings underscore the potential of DCLK1 as a colorectal cancer biomarker for early detection, but may also have clinical implications regarding the previously proposed therapy toward DCLK1-positive cancer cells. This therapy would at best affect the cancer stem cell population, but will, based on the present results, not be efficient to treat the bulk of the tumor.
authors.affiliation: Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital-Norwegian Radium Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Hege Marie
authors.initials: HM
authors.lastname: Vedeld
authors.affiliation: Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital-Norwegian Radium Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Rolf I
authors.initials: RI
authors.lastname: Skotheim
authors.affiliation: Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital-Norwegian Radium Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.affiliation: Department of Cancer Prevention; Institute for Cancer Research; Oslo University Hospital-Norwegian Radium Hospital; Oslo, Norway; Centre for Cancer Biomedicine; University of Oslo; Oslo, Norway.
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D000089742:Doublecortin-Like Kinases; D044127:Epigenesis, Genetic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012007:Rectum / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D012313:RNA; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases
keywords: DCLK1; DNA methylation; biomarker; colorectal cancer