CONTEXT: CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels. OBJECTIVE: To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels. DESIGN: We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction. RESULTS: With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability-negative colorectal cancers had the worst clinical outcomes. CONCLUSIONS: Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.
CONTEXT: CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels. OBJECTIVE: To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels. DESIGN: We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction. RESULTS: With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability-negative colorectal cancers had the worst clinical outcomes. CONCLUSIONS: Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.
Authors: Orsolya Galamb; Alexandra Kalmár; Bálint Péterfia; István Csabai; András Bodor; Dezső Ribli; Tibor Krenács; Árpád V Patai; Barnabás Wichmann; Barbara Kinga Barták; Kinga Tóth; Gábor Valcz; Sándor Spisák; Zsolt Tulassay; Béla Molnár Journal: Epigenetics Date: 2016-05-31 Impact factor: 4.528
Authors: Vera Kloten; Michael Rose; Sophie Kaspar; Saskia von Stillfried; Ruth Knüchel; Edgar Dahl Journal: Epigenetics Date: 2014-08-04 Impact factor: 4.528
Authors: N Jewel Samadder; Robert A Vierkant; Lori S Tillmans; Alice H Wang; Daniel J Weisenberger; Peter W Laird; Charles F Lynch; Kristin E Anderson; Amy J French; Robert W Haile; John D Potter; Susan L Slager; Thomas C Smyrk; Stephen N Thibodeau; James R Cerhan; Paul J Limburg Journal: Gastroenterology Date: 2013-05-07 Impact factor: 22.682