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Comparative Study
. 2019 Jul 19;9(1):10516.
doi: 10.1038/s41598-019-47014-w.

Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

Sandra Tapial  1   2 , Susana Olmedillas-López  3 , Daniel Rueda  1   2 , María Arriba  4 , Juan L García  5   6 , Alfredo Vivas  7 , Jessica Pérez  5   6 , Laura Pena-Couso  8 , Rocío Olivera  3 , Yolanda Rodríguez  9 , Mariano García-Arranz  3 , Damián García-Olmo  3   10 , Rogelio González-Sarmiento  11   12 , Miguel Urioste  8   13 , Ajay Goel  14 , José Perea  15
Affiliations
Comparative Study

Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers

Sandra Tapial et al. Sci Rep. .

Abstract

Colorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a "unique" CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Sample showing Microsatellite stability (above) and other showing Microsatellite instability (below).
Figure 2
Figure 2
Sample with wild-type KRAS (above), other sample with codon 13 mutation (medium), and the last with codon 12 mutation (below), seen in the Integrative Genomics Viewer by Next Generation Sequencing.
Figure 3
Figure 3
(A) Sample with CpG Island Methylator Phenotype negative (CIMP−). (B) Sample with CpG Island Methylator Phenotype positive (CIMP+).
Figure 4
Figure 4
Number of methylated genes in each tumor of (a) EOCRC patients; (b) LOCRC patients; (c) SCRC patients; (d) MCRC patients.
See this image and copyright information in PMC

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