Meessen Sabine, Currey Nicola, Jahan Zeenat, Parker Hannah W, Jenkins Mark A, Buchanan Daniel D, Hopper John L, Segelov Eva, Dahlstrom Jane E, Kohonen-Corish Maija R J
Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
The Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW 2037, Australia.
Cancers (Basel). 2021 Jul 14;13(14):3529. doi: 10.3390/cancers13143529.
gene or protein deficiency or loss-of-function in colorectal cancer can cause a DNA mismatch repair defect known as "elevated microsatellite alterations at selected tetranucleotide repeats" (EMAST). A high percentage of MSI-H tumors exhibit EMAST, while MSI-L is also linked with EMAST. However, the distribution of CpG island methylator phenotype (CIMP) within the EMAST spectrum is not known. Five tetranucleotide repeat and five MSI markers were used to classify 100 sporadic colorectal tumours for EMAST, MSI-H and MSI-L according to the number of unstable markers detected. Promoter methylation was determined using methylation-specific PCR for , , (p16) and five CIMP marker genes. EMAST was found in 55% of sporadic colorectal carcinomas. Carcinomas with only one positive marker (EMAST-1/5, 26%) were associated with advanced tumour stage, increased lymph node metastasis, MSI-L and lack of CIMP-H. EMAST-2/5 (16%) carcinomas displayed some methylation but MSI was rare. Carcinomas with 3 positive EMAST markers (13%) were more likely to have a proximal colon location and be MSI-H and CIMP-H. Our study suggests that EMAST/MSI-L is a valuable prognostic and predictive marker for colorectal carcinomas that do not display the high methylation phenotype CIMP-H.
结直肠癌中的基因或蛋白质缺陷或功能丧失可导致一种称为“选定四核苷酸重复序列处微卫星改变增加”（EMAST）的DNA错配修复缺陷。高比例的微卫星高度不稳定（MSI-H）肿瘤表现出EMAST，而微卫星低度不稳定（MSI-L）也与EMAST有关。然而，EMAST谱内CpG岛甲基化表型（CIMP）的分布尚不清楚。使用五个四核苷酸重复序列和五个MSI标记，根据检测到的不稳定标记数量，对100例散发性结直肠癌进行EMAST、MSI-H和MSI-L分类。使用甲基化特异性PCR检测、、（p16）和五个CIMP标记基因的启动子甲基化。在55%的散发性结直肠癌中发现了EMAST。仅有一个阳性标记（EMAST-1/5，26%）的癌与肿瘤晚期、淋巴结转移增加、MSI-L和缺乏CIMP-H相关。EMAST-2/5（16%）的癌显示出一些甲基化，但MSI罕见。有3个阳性EMAST标记的癌（13%）更有可能位于近端结肠，且为MSI-H和CIMP-H。我们的研究表明，对于未表现出高甲基化表型CIMP-H的结直肠癌，EMAST/MSI-L是一种有价值的预后和预测标志物。
