WRN promoter methylation possibly connects mucinous differentiation, microsatellite instability and CpG island methylator phenotype in colorectal cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-12-14

AUTHORS

Takako Kawasaki, Mutsuko Ohnishi, Yuko Suemoto, Gregory J Kirkner, Zhiqian Liu, Hiroyuki Yamamoto, Massimo Loda, Charles S Fuchs, Shuji Ogino

ABSTRACT

Werner syndrome is a premature aging syndrome characterized by early onset of cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase plays an important role in the maintenance of telomere function. WRN promoter methylation and gene silencing are common in colorectal cancer with the CpG island methylator phenotype (CIMP), which is associated with microsatellite instability (MSI) and mucinous tumors. However, no study has examined the relationship between mucinous differentiation, WRN methylation, CIMP and MSI in colorectal cancer. Utilizing 903 population-based colorectal cancers and real-time PCR (MethyLight), we quantified DNA methylation in WRN and eight other promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) known to be specific for CIMP. Supporting WRN as a good CIMP marker, WRN methylation was correlated well with CIMP-high diagnosis (≥6/8 methylated promoters), demonstrating 89% sensitivity and 81% specificity. WRN methylation was associated with the presence of any mucinous component and ≥50% mucinous component (P<0.0001). Because both MSI and CIMP were associated with mucinous tumors and WRN methylation, we stratified tumors into 9 MSI/CIMP subtypes, to examine whether the relationship between WRN methylation and mucin still persisted. In each MSI/CIMP subtype, tumors with mucinous component were persistently more common in WRN-methylated tumors than WRN-unmethylated tumors (P=0.004). No relations of WRN methylation with other variables (age, sex, tumor location, poor differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21 or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP status. In conclusion, WRN methylation is associated with mucinous differentiation independent of CIMP and MSI status. Our data suggest a possible role of WRN methylation in mucinous differentiation, and may provide explanation to the enigmatic association between mucin and MSI/CIMP. More... »

PAGES

150-158

References to SciGraph publications

  • 2006-06-25. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer in NATURE GENETICS
  • 2004-09-24. Progressive methylation during the serrated neoplasia pathway of the colorectum in MODERN PATHOLOGY
  • 1985. Acidic Glycosaminoglycans of SV40-Transformed Werner’s Syndrome Cells in WERNER’S SYNDROME AND HUMAN AGING
  • 2007-04-27. DNA methylation in breast and colorectal cancers in MODERN PATHOLOGY
  • 1985. Glycosaminoglycan Synthesis in Untransformed and Transformed Werner Syndrome Fibroblasts: A Preliminary Report in WERNER’S SYNDROME AND HUMAN AGING
  • 2005-08-12. Distinct molecular features of colorectal carcinoma with signet ring cell component and colorectal carcinoma with mucinous component in MODERN PATHOLOGY
  • 2005-10-21. DNA hypermethylation status of multiple genes in soft tissue sarcomas in MODERN PATHOLOGY
  • 1997-09. The Werner syndrome protein is a DNA helicase in NATURE GENETICS
  • 2004-07-04. Essential role of limiting telomeres in the pathogenesis of Werner syndrome in NATURE GENETICS
  • 2006-11-03. Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP in MODERN PATHOLOGY
  • 2000-12-01. Validation of Tissue Microarray Technology in Breast Carcinoma in LABORATORY INVESTIGATION
  • 1997-01. Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA in NATURE
  • 2005-05-01. The Nurses' Health Study: lifestyle and health among women in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/modpathol.3800996

    DOI

    http://dx.doi.org/10.1038/modpathol.3800996

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012871709

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18084250


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    38 schema:description Werner syndrome is a premature aging syndrome characterized by early onset of cancer and abnormal cellular metabolism of glycosaminoglycan. The WRN helicase plays an important role in the maintenance of telomere function. WRN promoter methylation and gene silencing are common in colorectal cancer with the CpG island methylator phenotype (CIMP), which is associated with microsatellite instability (MSI) and mucinous tumors. However, no study has examined the relationship between mucinous differentiation, WRN methylation, CIMP and MSI in colorectal cancer. Utilizing 903 population-based colorectal cancers and real-time PCR (MethyLight), we quantified DNA methylation in WRN and eight other promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) known to be specific for CIMP. Supporting WRN as a good CIMP marker, WRN methylation was correlated well with CIMP-high diagnosis (≥6/8 methylated promoters), demonstrating 89% sensitivity and 81% specificity. WRN methylation was associated with the presence of any mucinous component and ≥50% mucinous component (P<0.0001). Because both MSI and CIMP were associated with mucinous tumors and WRN methylation, we stratified tumors into 9 MSI/CIMP subtypes, to examine whether the relationship between WRN methylation and mucin still persisted. In each MSI/CIMP subtype, tumors with mucinous component were persistently more common in WRN-methylated tumors than WRN-unmethylated tumors (P=0.004). No relations of WRN methylation with other variables (age, sex, tumor location, poor differentiation, signet ring cells, lymphocytic reactions, KRAS, BRAF, p53, p21 or 18q loss of heterozygosity) persisted after tumors were stratified by CIMP status. In conclusion, WRN methylation is associated with mucinous differentiation independent of CIMP and MSI status. Our data suggest a possible role of WRN methylation in mucinous differentiation, and may provide explanation to the enigmatic association between mucin and MSI/CIMP.
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