Aravena Tania Isabella, Valdés Elizabeth, Ayala Nicolás, D'Afonseca Vívian
Facultad de Ciencias Agrarias y Forestales, Universidad Católica del Maule, Talca, Chile.
Departamento de Genética, Microbiología y Estadística, Universidad de Barcelona, España.
Cancer Inform. 2023 Mar 29;22:11769351231161480. doi: 10.1177/11769351231161480. eCollection 2023.
Histone methyltransferases (HMTs) comprise a subclass of epigenetic regulators. Dysregulation of these enzymes results in aberrant epigenetic regulation, commonly observed in various tumor types, including hepatocellular adenocarcinoma (HCC). Probably, these epigenetic changes could lead to tumorigenesis processes. To predict how histone methyltransferase genes and their genetic alterations (somatic mutations, somatic copy number alterations, and gene expression changes) are involved in hepatocellular adenocarcinoma processes, we performed an integrated computational analysis of genetic alterations in 50 HMT genes present in hepatocellular adenocarcinoma. Biological data were obtained through the public repository with 360 samples from patients with hepatocellular carcinoma. Through these biological data, we identified 10 HMT genes (, and ) with a significant genetic alteration rate (14%) within 360 samples. Of these 10 HMT genes, and have the highest mutation rate in HCC samples, 5.6% and 2.8%, respectively. Regarding somatic copy number alteration, and are amplified in several samples, while , and showed a high rate of large deletion. Finally, , and could play an important role in the progression of hepatocellular adenocarcinoma since alterations in these genes lead to a decrease in patient survival, unlike patients who present these genes without genetic alterations. Our computational analysis provides new insights that help to understand how HMTs are associated with hepatocellular carcinoma, as well as provide a basis for future experimental investigations using HMTs as genetic targets against hepatocellular carcinoma.
组蛋白甲基转移酶（HMTs）是表观遗传调节因子的一个亚类。这些酶的失调会导致异常的表观遗传调控，这在包括肝细胞癌（HCC）在内的各种肿瘤类型中普遍存在。这些表观遗传变化可能会导致肿瘤发生过程。为了预测组蛋白甲基转移酶基因及其遗传改变（体细胞突变、体细胞拷贝数改变和基因表达变化）如何参与肝细胞癌的发生过程，我们对肝细胞癌中存在的50个HMT基因的遗传改变进行了综合计算分析。生物数据是通过公共数据库从360例肝细胞癌患者样本中获得的。通过这些生物数据，我们在360个样本中鉴定出10个具有显著遗传改变率（14%）的HMT基因（、和）。在这10个HMT基因中，和在HCC样本中的突变率最高，分别为5.6%和2.8%。关于体细胞拷贝数改变，和在几个样本中扩增，而、和显示出高频率的大片段缺失。最后，、和可能在肝细胞癌的进展中起重要作用，因为这些基因的改变会导致患者生存率下降，这与那些没有遗传改变的携带这些基因的患者不同。我们的计算分析提供了新的见解，有助于理解HMTs如何与肝细胞癌相关联，并为未来以HMTs作为针对肝细胞癌的遗传靶点的实验研究提供了基础。
