Departments of Pathology and Cancer Research Institute, Seoul, Korea.
College of Medicine, The Catholic University of Korea, Seoul, Korea.
Pathol Oncol Res. 2021 Apr 14;27:625438. doi: 10.3389/pore.2021.625438. eCollection 2021.
and genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of and in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed and frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified and frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in and mutations, respectively. In the multi-region samples of 23 MSS CCs, neither nor frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that and frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.
肿瘤坏死因子受体(TNF-R)相关因子(TRAF)家族的基因参与多种细胞信号转导,既作为肿瘤抑制基因又作为癌基因发挥作用。结肠癌(CC)中 和 的改变及其区域差异和微卫星不稳定性(MSI)在很大程度上尚不清楚。在本研究中,我们分析了 168 例散发性 CC 中的 和 移码突变(100 例高 MSI(MSI-H)和 68 例微卫星稳定(MSS)CC)。我们分别在 4 例(4%)和 3 例(3%)MSI-H CC 中发现了 和 移码突变,但在 68 例 MSS CC 中均未发现。在 168 例 CC 中,我们对 39 例 CC(16 例 MSI-H 和 23 例 MSS CC)的多个区域进行了突变分析,发现 12.5%(2/16)和 6.3%(1/16)的 MSI-H CC 存在 和 突变的区域差异。在 23 例 MSS CC 的多区域样本中,既未发现 也未发现 移码突变。在 40%的 CC 中,与正常结肠细胞相比,TRAF2 和 TRAF3 的表达均增加。我们的数据表明,MSI-H CC 中存在 和 移码突变及其区域差异以及改变的表达,这可能有助于 MSI-H 癌症的发展。