Digestive Cancer Research Group, 12 de Octubre Research Institute, Madrid, Spain.
Hereditary Cancer Laboratory, 12 de Octubre University Hospital, Madrid, Spain.
Sci Rep. 2019 Jul 19;9(1):10516. doi: 10.1038/s41598-019-47014-w.
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.
结直肠癌(CRC)伴 CpG 岛甲基化表型(CIMP)被认为是 CRC 的一个亚组,其与特定的遗传缺陷和患者预后相关。我们使用 8 个标志物(CACNA1G、CDKN2A、CRABP1、IGF2、MLH1、NEUROG1、RUNX3 和 SOCS1)对 229 名 CRC 患者进行了 CIMP 状态分析;CIMP(+)肿瘤定义为有≥5 个甲基化标志物。将患者分为发生“独特”CRC 的个体,进一步细分为早发性 CRC(EOCRC)和晚发性 CRC(LOCRC),以及多发性原发性 CRC 患者,细分为同步性 CRC(SCRC)和异时性 CRC(MCRC)。我们发现 9 例(15.2%)CIMP(+) EOCRC 患者与近端结肠相关(p=0.008),19 例(26.8%)CIMP(+) LOCRC 患者与肿瘤分化(p=0.045)、微卫星不稳定性(MSI)状态(p=0.021)和 BRAF 突变(p=0.001)相关。35 例(64.8%)SCRC 患者至少有一个 CIMP(+)肿瘤,20 例(44.4%)MCRC 患者首次肿瘤为 CIMP(+)。39 例(72.2%)SCRC 患者同时性肿瘤的 CIMP 状态一致。各组间 CIMP(+)频率的差异可能反映了考虑多种标准来发展多发性原发性肿瘤的重要性。此外,同步性肿瘤的一致性表明 CIMP 状态在 SCRC 患者中通常保持一致。