Histology and Genetic Section, Department of Clinical Pathology, National Cancer Institute, Cairo University, Egypt.
Clinical Pathology and Oncologic, Department of Laboratory Medicine, National Cancer Institute, Cairo University, Egypt.
Asian Pac J Cancer Prev. 2023 Sep 1;24(9):3169-3182. doi: 10.31557/APJCP.2023.24.9.3169.
Isocitrate dehydrogenase genes (IDH1 and IDH2) encode important enzymes that play pivotal role in cellular metabolism. Mutations in TET2 have been demonstrated to contribute to DNA hypermethylation, either expression of mutant IDH1/2 or TET2 resulted in poor cell differentiation and epigenetic alterations in hematopoietic cells, suggesting a sharing of the oncogenetic impact. In this study, we investigated the frequency of genetic alterations in IDH1/2 and TET2 genes in Egyptian cohort of adult patients with de novo AML, and the association of IDH1/2 and TET2 genetic Polymorphism with AML prognostic criteria and explore prognostic molecular markers with clinical outcome.
The SNP assay for IDH1, IDH2 and TET2 genes polymorphism tested with RT-PCR included three polymorphisms that are rs121913500, rs121913503, and rs2454206 respectively, were tested on 141 adult Egyptian patients fulfilling the AML diagnostic criteria.
The incidence of IDH mutations is 11/141 (7.8%); 5/141 (3.5%) IDH1 mutant and 6/141 (4.3%) IDH2 mutant. And the incidence of TET2 mutations is 72/141 (51.1%); 15/141 (10.7%) homozygous mutation and 57/141 (40.4%) heterozygous mutations. IDH1, IDH2 and TET2 genes mutations with DFS and OS in AML patients were not significantly correlated.
TET2 SNP is common in Egyptian AML patients. Further research on IDH, TET2 and their relationships to other hematological malignancies and leukemogenesis transformation is advised and a study of a larger number of cases is needed for potential statistical significance.
异柠檬酸脱氢酶基因（IDH1 和 IDH2）编码在细胞代谢中起关键作用的重要酶。已经证明 TET2 中的突变导致 DNA 超甲基化，突变 IDH1/2 或 TET2 的表达导致造血细胞分化不良和表观遗传改变，表明存在致癌基因的共同影响。在本研究中，我们调查了 IDH1/2 和 TET2 基因在埃及初发 AML 成人患者中的遗传改变频率，以及 IDH1/2 和 TET2 基因遗传多态性与 AML 预后标准的关系，并探索与临床结果相关的预后分子标志物。
采用 RT-PCR 检测 IDH1、IDH2 和 TET2 基因多态性的 SNP 检测，包括 rs121913500、rs121913503 和 rs2454206 三个多态性，共检测了 141 例符合 AML 诊断标准的埃及成年患者。
IDH 突变的发生率为 11/141（7.8%）；5/141（3.5%）为 IDH1 突变，6/141（4.3%）为 IDH2 突变。TET2 突变的发生率为 72/141（51.1%）；15/141（10.7%）为纯合突变，57/141（40.4%）为杂合突变。IDH1、IDH2 和 TET2 基因突变与 AML 患者的 DFS 和 OS 无显著相关性。
TET2 SNP 在埃及 AML 患者中较为常见。建议进一步研究 IDH、TET2 及其与其他血液恶性肿瘤和白血病转化的关系，并需要对更多病例进行研究以获得潜在的统计学意义。
