Epigenetic markers stratify colorectal cancer patients within a genetically defined poor prognostic patient group
Vedeld and co-workers show that the CpG Island Methylator Phenotype (CIMP) carry prognostic value across stages. Patients with microsatellite stable tumors with BRAF V600E mutations, defining a poor prognostic subgroup, can be further subdivided by the CIMP status. This is a study from the Lind and Lothe groups in collaboration with the clinical research team of Arild Nesbakken.
The majority of primary colorectal cancers are microsatellite stable (MSS). Among these, BRAF mutations constitute a subgroup of patients with poor prognosis. The CpG Island methylator phenotype (CIMP) is characterized by widespread promoter hypermethylation, and has been suggested to confer an inferior survival. Limited samples sizes, qualitative methods and different marker panels to define CIMP have, however, restricted robust analyzes, specifically within patients subgroups. Vedeld and colleagues analyzed the prognostic value of CIMP in two Norwegian population representative patient series (n>1100), using a well-established and validated CIMP panel. In stratified analyses, CIMP tumors showed significantly worse outcome among patients with MSS and MSS BRAF mutated tumors, a finding that persisted in patients with stage II, III or IV disease, and that remained significant in multivariate analysis. This study shows for the first time that CIMP can further stratify the poor prognostic group of patients with MSS BRAF mutated tumors, and thus identify a subgroup of patients with a particularly poor prognosis.