Departments of Pathology.
General Surgery.
Appl Immunohistochem Mol Morphol. 2021 Sep 1;29(8):570-575. doi: 10.1097/PAI.0000000000000939.
ZMYM4 is a zinc finger protein, whose cancer-related functions are partially known (cell shape maintenance and cell death). In this study, we analyzed 4 sites of mononucleotide repeats in the coding sequence of ZMYM4 in gastric (GC) and colonic cancers (CC). Seven of the 32 high microsatellite instability (MSI-H) GCs (21.9%) and 23 of 113 MSI-H CCs (20.4%) harbored ZMYM4 frameshift mutations with no significant difference between the 2 organs (P>0.05). There was no ZMYM4 frameshift mutations in microsatellite-stable GCs and CCs. We also identified that 6 of 16 MSI-H CCs (37.5%) exhibited intratumoral heterogeneity of the ZMYM4 frameshift mutations. In both GC and CC with MSI-H, ZMYM4 expression in ZMYM4-mutated cases was significantly lower than that in ZMYM4-nonmutated cases. Our study indicates that ZMYM4 is altered at multiple levels (frameshift mutation, mutational intratumoral heterogeneity, and loss of expression), suggesting their relations with MSI-H GC and CC.
ZMYM4 是一种锌指蛋白，其与癌症相关的功能部分已知（维持细胞形态和细胞死亡）。在这项研究中，我们分析了胃（GC）和结肠（CC）癌症中 ZMYM4 编码序列中 4 个单核苷酸重复序列位点。32 个高微卫星不稳定性（MSI-H）GC 中有 7 个（21.9%）和 113 个 MSI-H CC 中有 23 个（20.4%）存在 ZMYM4 移码突变，两个器官之间没有显著差异（P>0.05）。微卫星稳定的 GC 和 CC 中没有 ZMYM4 移码突变。我们还发现，16 个 MSI-H CC 中有 6 个（37.5%）表现出 ZMYM4 移码突变的肿瘤内异质性。在 MSI-H 的 GC 和 CC 中，ZMYM4 突变病例中的 ZMYM4 表达明显低于 ZMYM4 非突变病例。我们的研究表明，ZMYM4 发生了多个层面的改变（移码突变、突变的肿瘤内异质性和表达缺失），提示其与 MSI-H GC 和 CC 有关。
