Department of Pharmaceutical Chemistry, College of Pharmacy, Northern Border University, 91911, Rafha, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Al-Abidiyah, P.O. Box 13578, 21955, Mecca, Saudi Arabia.
Med Oncol. 2024 Oct 17;41(11):290. doi: 10.1007/s12032-024-02532-0.
Pheochromocytomas and paragangliomas (PCCs/PGLs) are uncommon neuroendocrine tumors with a significant genetic tendency. Approximately 35-40% of these tumors are associated with genetic factors. The present study performed a thorough analysis using publicly accessible genetic and clinical data from the Cancer Genome Atlas (TCGA) to examine the involvement of six genes, namely GBP1, KIF13B, GPT, CSDE1, CEP164, and CLCA1, in the development of PCCs/PGLs. By employing multi-omics data, this study investigates the relationship between mutational patterns and the prognosis of tumors, focusing on the possibility of tailoring treatment methods to individual patients. The study utilizes Mutect2 to detect somatic mutations with high confidence in whole-exome sequencing data from PCCG samples. The study uncovers mild effects on protein function caused by particular mutations, including GBP1 (p.Cys12Tyr), KIF13B (p.Arg847Gly), and GPT (p.Gln50Arg). A random forest classifier uses mutational profiles to predict potential drug recommendations, proposing a focused therapy strategy. This study thoroughly analyzes the genetic mutations found in PCCs/PGLs, highlighting the significance of precision medicine in developing specific treatments for these uncommon types of cancer. This study aims to improve the understanding of the development of tumors and identify personalized treatment approaches by combining genetic data with machine learning analyses.
嗜铬细胞瘤和副神经节瘤(PCCs/PGLs)是罕见的神经内分泌肿瘤,具有显著的遗传倾向。这些肿瘤中约有 35-40%与遗传因素有关。本研究利用癌症基因组图谱(TCGA)中公开的遗传和临床数据进行了全面分析,以检查六个基因(GBP1、KIF13B、GPT、CSDE1、CEP164 和 CLCA1)在 PCCs/PGLs 发展中的作用。通过多组学数据,本研究探讨了突变模式与肿瘤预后之间的关系,重点关注为个体患者定制治疗方法的可能性。该研究使用 Mutect2 在 PCCG 样本的全外显子测序数据中以高可信度检测体细胞突变。该研究揭示了特定突变对蛋白质功能的轻微影响,包括 GBP1(p.Cys12Tyr)、KIF13B(p.Arg847Gly)和 GPT(p.Gln50Arg)。随机森林分类器使用突变谱来预测潜在的药物推荐,提出了一种集中治疗策略。本研究全面分析了 PCCs/PGLs 中发现的遗传突变,强调了精准医学在为这些罕见类型的癌症开发特定治疗方法中的重要性。本研究旨在通过将遗传数据与机器学习分析相结合,提高对肿瘤发展的理解,并确定个性化的治疗方法。