Laboratory of Oncovirology Cancer Research Institute Tomsk NMRC, Tomsk, Russia; National Research Tomsk State University, Tomsk, Russia.
Laboratory of Oncovirology Cancer Research Institute Tomsk NMRC, Tomsk, Russia; National Research Tomsk State University, Tomsk, Russia.
Curr Probl Cancer. 2020 Oct;44(5):100567. doi: 10.1016/j.currproblcancer.2020.100567. Epub 2020 Mar 17.
In 5 patients, a change in the genetic landscape from HPV16 positive high-grade squamous intraepithelial lesion (HSIL) to squamous cervical cancer was traced, which occurred in these patients within the period from 7 months to 5 years after diagnosing HSIL.
The DNA from paraffin blocks of dysplasia tissue and the tumor that emerged afterwards was used for the study, which was analyzed using the OncoScan FFPE microarray Assay Kit Affymetrix (USA) for genome-wide determination of gene abundance and 65 key somatic driver mutations of oncogenes and tumor suppressor genes.
In the study of HSIL material, somatic mutations were observed in 4/5 cases, 18 different somatic driver mutations of the NRAS, EGFR, BRAF, KRAS, IDH2 oncogenes and TP53 suppressor genes were found and almost no CNA-Copy Number Aberration was identified. HSIL malignization is associated with the appearance of secondary driver mutations in oncogenes and tumor suppressor genes and a large number of structural and numerical CNA, the frequency of which correlates with the time of dysplasia malignization into cancer with a very high correlation coefficient r = 0.98, P = 0.004. The trees of dysplasia evolution into tumor were constructed for each patient.
According to the results of the work, it is assumed that the initiation of the development of mucosa dysplastic changes is due to primary driver mutations. The formation of secondary driver mutations and CNA are genetic mechanisms of malignant transformation, while the scenarios of the evolution of dysplasia into a tumor are individual and very diverse.
在 5 名患者中，追踪到 HPV16 阳性高级别鳞状上皮内病变（HSIL）到鳞状宫颈癌的遗传景观发生变化，这些患者在诊断为 HSIL 后 7 个月至 5 年内发生。
使用来自发育不良组织和随后出现的肿瘤的石蜡块中的 DNA 进行研究，使用 Affymetrix（美国）的 OncoScan FFPE microarray Assay Kit 进行全基因组基因丰度和 65 个致癌基因和肿瘤抑制基因的关键体细胞驱动突变分析。
在 HSIL 材料的研究中，观察到 4/5 例存在体细胞突变，发现了 NRAS、EGFR、BRAF、KRAS、IDH2 癌基因和 TP53 肿瘤抑制基因的 18 种不同的体细胞驱动突变，几乎没有 CNA-Copy Number Aberration。HSIL 恶变与癌基因和肿瘤抑制基因中继发性驱动突变的出现以及大量结构和数量 CNA 相关，其频率与发育不良恶变至癌症的时间相关，相关性系数 r 非常高= 0.98，P = 0.004。为每位患者构建了发育不良进化为肿瘤的树。
根据工作结果，假设黏膜发育不良变化的发生是由于原发性驱动突变引起的。继发性驱动突变和 CNA 的形成是恶性转化的遗传机制，而发育不良向肿瘤的进化场景是个体的，非常多样化。
