Departments of Pathology.
Biomedicine & Health Sciences.
Appl Immunohistochem Mol Morphol. 2022 Feb 1;30(2):e16-e20. doi: 10.1097/PAI.0000000000000989.
Deregulations of DNA-methylation-related genes are common in cancers, but frameshift mutation status in colon cancer (CC) is unknown. Our study aims to assess whether CTCF, ZFP57, and ATF7IP genes in this category are mutated in CC. CTCF, ZFP57, and ATF7IP genes have repeat coding sequences, which are frequently deleted or duplicated in CC, harboring the phenotype of unstable or high microsatellite instability (MSI-H). We studied 140 CCs [95 MSI-H CCs and 45 stable MSI (MSS) CCs], and found 7 CCs with MSI-H (6/95: 6.3%) harbored frameshift mutations within the repeats, whereas those with MSS did not. Of note, the CTCF frameshift mutations showed the regional difference in the 2 (12.5%) of 16 MSI-H CCs, indicating there was intratumoral heterogeneity. In the immunohistochemistry for ATF7IP, the MSI-H CC showed low intensity compared to MSS CC. Together, CTCF, ZFP57, and ATF7IP genes, despite the low incidence of the mutations, are altered in several ways (mutation, expression, and intratumoral heterogeneity) and could contribute to MSI-H CC development.
DNA 甲基化相关基因的失调在癌症中很常见，但结肠癌（CC）中的移码突变状态尚不清楚。我们的研究旨在评估 CTCF、ZFP57 和 ATF7IP 这一类基因在 CC 中是否发生了突变。CTCF、ZFP57 和 ATF7IP 基因具有重复编码序列，这些序列在 CC 中经常缺失或重复，具有不稳定或高微卫星不稳定性（MSI-H）的表型。我们研究了 140 例 CC[95 例 MSI-H CC 和 45 例稳定 MSI（MSS）CC]，发现 7 例 MSI-H（6/95：6.3%）的 CC 中存在重复序列内的移码突变，而 MSS 则没有。值得注意的是，在 16 例 MSI-H CC 中的 2 例（12.5%）中，CTCF 的移码突变显示出区域性差异，表明存在肿瘤内异质性。在 ATF7IP 的免疫组化中，MSI-H CC 的染色强度低于 MSS CC。总之，尽管突变发生率较低，但 CTCF、ZFP57 和 ATF7IP 基因在多个方面发生了改变（突变、表达和肿瘤内异质性），并可能有助于 MSI-H CC 的发生发展。
