TY - JOUR
T1 - CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer
AU - Cleven, Arjen H G
AU - Derks, Sarah
AU - Draht, Muriel X G
AU - Smits, Kim M.
AU - Melotte, Veerle
AU - Van Neste, Leander
AU - Tournier, Benjamin
AU - Jooste, Valerie
AU - Chapusot, Caroline
AU - Weijenberg, Matty P.
AU - Herman, James G.
AU - De Bruïne, Adriaan P.
AU - Van Engeland, Manon
PY - 2014/6/15
Y1 - 2014/6/15
N2 - 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 =
AB - 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 =
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U2 - 10.1158/1078-0432.CCR-12-3734
DO - 10.1158/1078-0432.CCR-12-3734
M3 - Article
C2 - 24928946
AN - SCOPUS:84902665588
SN - 1078-0432
VL - 20
SP - 3261
EP - 3271
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -