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Multiregional assessment of CIMP in primary colorectal cancers: Phenotype concordance but marker variability
Author(s) -
Flatin Bjørnar T.B.,
Vedeld Hege Marie,
Pinto Rita,
Langerud Jonas,
Lind Guro E.,
Lothe Ragnhild A.,
Sveen Anita,
Jeanmougin Marine
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.33425
Subject(s) - biology , dna methylation , epigenetics , methylation , epigenomics , phenotype , carcinogenesis , cancer research , concordance , genetics , gene , gene expression
Intratumor heterogeneity of colorectal cancers (CRCs) is manifested both at the genomic and epigenomic levels. Early genetic aberrations in carcinogenesis are clonal and present throughout the tumors, but less is known about the heterogeneity of the epigenetic CpG island methylator phenotype (CIMP). CIMP characterizes a subgroup of CRCs thought to originate from specific precursor lesions, and it is defined by widespread DNA methylation within promoter regions. In this work, we investigated CIMP in two to four multiregional samples from 30 primary tumors (n = 86 samples) using the consensus Weisenberger gene panel ( CACNA1G , IGF2 , NEUROG1 , RUNX3 and SOCS1 ). Twenty‐nine of 30 tumors (97%) showed concordant CIMP status in all samples, and percent methylated reference (PMR) values of all five markers had higher intertumor than intratumor variation ( P value = 1.5e−09). However, a third of the CIMP+ tumors exhibited discrepancies in methylation status in at least one of the five gene markers. To conclude, CIMP status was consistent within primary CRCs, and it is likely a clonal phenotype. However, spatial discordances of the individual genes suggest that large‐scale analysis of multiregional samples could be of interest for identifying CIMP markers that are robust to intratumor heterogeneity.