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.
CpG island methylator phenotype identifies high risk patients among microsatellite stable BRAF mutated colorectal cancers.
Vedeld HM, Merok M, Jeanmougin M, Danielsen SA, Honne H, Presthus GK, Svindland A, Sjo OH, Hektoen M, Eknaes M, Nesbakken A, Lothe RA, Lind GE.
Int J Cancer. 2017 May 20. [Epub ahead of print]
Latest publicationsSveen et al. 2019. Predictive modeling in colorectal cancer: time to move beyond consensus molecular subtypes. Ann. Oncol. 30(11): 1682-1685 Miranda et al. 2019. Cancer stemness, intratumoral heterogeneity, and immune response across cancers. PNAS 116(18): 9020-9029 Burocziova et al. 2019. Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon. Cell Death. Dis. 10(11): 818
Eilertsen et al. 2019. Technical differences between sequencing and microarray platforms impact transcriptomic subtyping of colorectal cancer. Cancer Lett. [Epub ahead of print] Lopes et al. 2019. Digital image analysis of multiplex fluorescence IHC in colorectal cancer recognizes the prognostic value of CDX2 and its negative correlation with SOX2. Lab. Invest. [Epub ahead of print] All publications