CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer

Arjen H G Cleven, Sarah Derks, Muriel X G Draht, Kim M. Smits, Veerle Melotte, Leander Van Neste, Benjamin Tournier, Valerie Jooste, Caroline Chapusot, Matty P. Weijenberg, James G. Herman, Adriaan P. De Bruïne, Manon Van Engeland

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here, we examine the prognostic impact of promoter methylation in patients with CRC treated with surgery alone in the context of microsatellite instability (MSI), BRAF and KRAS mutations. Experimental Methods: One hundred and seventy-three CRCs were analyzed for promoter methylation of 19 tumor suppressor andDNArepair genes, the CpGisland methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations. Results: Unsupervised hierarchical clustering based on methylation status of 19 genes revealed three subgroups: cluster 1 [CL1, 57% (98/173) of CRCs], cluster 2 [CL2, 25% (43/173) of CRCs], and cluster 3 [CL3, 18% (32/173) of CRCs]. CL3 had the highest methylation index (0.25, 0.49, and 0.69, respectively, P =

Original languageEnglish (US)
Pages (from-to)3261-3271
Number of pages11
JournalClinical Cancer Research
Volume20
Issue number12
DOIs
StatePublished - Jun 15 2014

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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