Department of Molecular Biology with General Chemistry and Biochemistry Course, Kazakh-Russian Medical University, Almaty, Republic of Kazakhstan.
Molecular Genetic Research Center, Kazakh Institute of Oncology and Radiology, Almaty, Republic of Kazakhstan.
Asian Pac J Cancer Prev. 2023 Nov 1;24(11):3939-3947. doi: 10.31557/APJCP.2023.24.11.3939.
Gastric and colorectal adenocarcinomas are prevalent malignancies characterized by mutations in genes such as p53, RAS, and MDM2, which play crucial roles in tumorigenesis and cancer progression. Understanding the specific mutational patterns and their implications in these cancers was essential for identifying potential therapeutic targets.
To identify the nature of mutational disorders in the p53, p21Waf1, RAS and MDM2 genes, depending on the degree of cell differentiation by adenocarcinomas of the gastrointestinal tract.
Genomic DNA was isolated from 200 samples of stomach tissue and 233 samples of colon and rectum adenocarcinomas. A total of 433 samples, including gastric adenocarcinomas, colon and rectum adenocarcinomas and adjacent tissues, were collected.
Genomic DNA was isolated, and mutational analysis of p53, RAS (HRAS, KRAS, NRAS), and MDM2 genes was performed using polymerase chain reaction, gel electrophoresis, and restriction enzyme analysis. The deletion of p53 exon-intron 5-6, as well as HRAS 12 and HRAS 61 mutations, were detected in 78% of poorly differentiated adenocarcinomas. The deletions of p53 exon-intron 7-9 - in 100% of moderately differentiated adenocarcinomas and 50-60% of adjacent tissues. The loss of WAF1 gene expression was registered in almost 90% of poorly differentiated adenocarcinomas and 20% of adjacent tissue samples. The KRAS and NRAS mutations in almost 63.9% of studied colon and rectal samples indicated autonomous cell growth. This explains the aggressive and metastatic growth of tumours and the ineffectiveness of growth factor inhibitors in colorectal cancer. Finding ways to influence specific substitutions in RAS genes could prevent and eliminate uncontrolled invasive tumour growth.
By identifying specific gene mutations and differences in genetic markers, the study provided insights for the development of targeted diagnostic methods and personalised treatment strategies, ultimately improving the clinical outcomes in the field of oncology.
胃和结直肠腺癌是常见的恶性肿瘤，其特征是 p53、RAS 和 MDM2 等基因的突变，这些突变在肿瘤发生和癌症进展中起着关键作用。了解这些癌症中特定的突变模式及其意义对于确定潜在的治疗靶点至关重要。
根据胃肠道腺癌的细胞分化程度，确定 p53、p21Waf1、RAS 和 MDM2 基因的突变紊乱性质。
从 200 个胃组织样本和 233 个结肠和直肠腺癌样本中分离基因组 DNA。共收集了 433 个样本，包括胃腺癌、结肠和直肠腺癌以及相邻组织。
分离基因组 DNA，采用聚合酶链反应、凝胶电泳和限制性内切酶分析对 p53、RAS（HRAS、KRAS、NRAS）和 MDM2 基因进行突变分析。在低分化腺癌中检测到 p53 外显子-内含子 5-6 的缺失，以及 HRAS 12 和 HRAS 61 的突变，占 78%。中分化腺癌中 p53 外显子-内含子 7-9 的缺失占 100%，而相邻组织的缺失占 50-60%。在几乎 90%的低分化腺癌和 20%的相邻组织样本中检测到 WAF1 基因表达缺失。在研究的结肠和直肠样本中，KRAS 和 NRAS 突变占近 63.9%，表明细胞自主生长。这解释了肿瘤的侵袭性和转移性生长，以及生长因子抑制剂在结直肠癌中的无效性。找到影响 RAS 基因特定取代的方法可能会预防和消除不受控制的侵袭性肿瘤生长。
通过确定特定的基因突变和遗传标记的差异，该研究为开发靶向诊断方法和个体化治疗策略提供了思路，最终改善了肿瘤学领域的临床结果。
