Flores-López Beatriz Armida, Ayala-Madrigal María de la Luz, Moreno-Ortiz José Miguel, Peregrina-Sandoval Jorge, Trujillo-Rojas Miguel Ángel, Venegas-Rodríguez José Luis, Hernández-Ramírez Rosario, Fernández-Galindo Martha Alejandra, Gutiérrez-Angulo Melva
Departamento de Biología Molecular y Genómica, Doctorado en Genética Humana e Instituto de Genética Humana "Dr. Enrique Corona Rivera", Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, Guadalajara 45200, Jalisco, Mexico.
Curr Issues Mol Biol. 2022 Aug 20;44(8):3770-3778. doi: 10.3390/cimb44080258.
Colorectal cancer is a heterogeneous disease with multiple genomic changes that influence the clinical management of patients; thus, the search for new molecular targets remains necessary. The aim of this study was to identify genetic variants in tumor tissues from Mexican patients with colorectal cancer, using massive parallel sequencing. A total of 4813 genes were analyzed in tumoral DNA from colorectal cancer patients, using the TruSight One Sequencing panel. From these, 192 variants with clinical associations were found distributed in 168 different genes, of which 46 variants had not been previous reported in the literature or databases, although genes harboring those variants had already been described in colorectal cancer. Enrichment analysis of the affected genes was performed using Reactome software; pathway over-representation showed significance for disease, signal transduction, and immune system subsets in all patients, while exclusive subsets such as DNA repair, autophagy, and RNA metabolism were also found. Those characteristics, whether individual or shared, could give tumors specific capabilities for survival, aggressiveness, or response to treatment. Our results can be useful for future investigations targeting specific characteristics of tumors in colorectal cancer patients. The identification of exclusive or common pathways in colorectal cancer patients could be important for better diagnosis and personalized cancer treatment.
结直肠癌是一种具有多种基因组变化的异质性疾病，这些变化会影响患者的临床管理；因此，寻找新的分子靶点仍然很有必要。本研究的目的是通过大规模平行测序，鉴定墨西哥结直肠癌患者肿瘤组织中的基因变异。使用TruSight One测序面板，对4813个基因进行了结直肠癌患者肿瘤DNA分析。从中发现了192个具有临床关联的变异，分布在168个不同基因中，其中46个变异在文献或数据库中未曾报道过，尽管携带这些变异的基因在结直肠癌中已有描述。使用Reactome软件对受影响的基因进行富集分析；通路过度表达在所有患者的疾病、信号转导和免疫系统亚组中显示出显著性，同时还发现了DNA修复、自噬和RNA代谢等独特亚组。这些特征，无论是个体特征还是共同特征，都可以赋予肿瘤特定的生存、侵袭性或对治疗反应的能力。我们的结果可能有助于未来针对结直肠癌患者肿瘤特定特征的研究。结直肠癌患者中独特或常见通路的鉴定对于更好的诊断和个性化癌症治疗可能很重要。
