Department of Microbiology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India.
Cellular and Molecular Research Centre, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India.
Gulf J Oncolog. 2021 Sep;1(37):36-41.
Cytochrome P450 (CYPs) are enzymes belonging to the family of heme-containing proteins, most commonly found in the endoplasmic reticulum and mitochondria. These enzymes catalyze a variety of functions including metabolism of steroids, fatty acids, natural compounds, drugs and carcinogenic chemicals. The inherent association of CYPs with disease conditions have turned the focus into the genetic alterations or variations associated with phenotypes such as drug responsiveness, chemical toxicity and bioconversion of procarcinogens to active carcinogens.
A total of 8 genes of the CYP3 family were analyzed, among which 4 genes were found to harbour gross abnormalities and variations. The genes CYP3A4, CYP3A5, CYP3A7, CYP3A43 showed a common pattern of gene amplification in a group of patients. Truncating and missense variants were also identified of which rs199908125 of CYP3A4 and rs768530577 of CYP3A5 were reported in different populations.
The present observation study utilizes several computational tools to identify and predict the possible outcomes of gene alterations in CYP3 family of genes with head and neck squamous cell carcinoma (HNSCC). cBioportal hosts an exhaustive collection of datasets of various cancers which was the primary source of analysis. Oncoprint data obtained was further analysed using tools such as PROVEAN, I-Mutant and gnomAD.
The gnomAD analysis revealed a few polymorphic rare variants with minor allele frequency less than 0.01, which could have a putative association with HNSCC. Five out of eight variants identified were found to be deleterious exhibiting decreased protein stability.
Further screening of the genetic abnormalities through experimental validation in different populations are warranted to derive an association between the gene identifiers and disease phenotype.
细胞色素 P450（CYPs）是一类血红素蛋白家族的酶，最常见于内质网和线粒体中。这些酶催化多种功能，包括类固醇、脂肪酸、天然化合物、药物和致癌化学物质的代谢。CYPs 与疾病状况的固有关联使得研究重点转向与药物反应性、化学毒性和前致癌物向活性致癌物的生物转化等表型相关的遗传改变或变异。
共分析了 CYP3 家族的 8 个基因，其中 4 个基因被发现存在严重的异常和变异。CYP3A4、CYP3A5、CYP3A7、CYP3A43 基因在一组患者中表现出基因扩增的共同模式。还鉴定出截断和错义变异，其中 CYP3A4 的 rs199908125 和 CYP3A5 的 rs768530577 已在不同人群中报道。
本观察研究利用几种计算工具来识别和预测 CYP3 家族基因与头颈部鳞状细胞癌（HNSCC）相关的基因改变的可能结果。cBioportal 拥有各种癌症数据集的详尽集合，这是分析的主要来源。进一步使用 PROVEAN、I-Mutant 和 gnomAD 等工具分析获得的 Oncoprint 数据。
gnomAD 分析显示了一些罕见的多态性变体，其次要等位基因频率小于 0.01，这可能与 HNSCC 有潜在关联。鉴定出的 8 个变体中有 5 个是有害的，表现出蛋白质稳定性降低。
需要通过在不同人群中进行实验验证进一步筛选遗传异常，以得出基因标识符与疾病表型之间的关联。
