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Molecular Profiling of Tumor Tissue in Mexican Patients with Colorectal Cancer

2023-02-16T18:32:47Z

Title: Molecular Profiling of Tumor Tissue in Mexican Patients with Colorectal Cancer Authors: 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 Abstract: Abstract 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. Description: Artículo

Interaction of CCND2, CDKN1A, and POLD3 Variants in Mexican Patients with Colorectal Cancer

2023-02-14T19:42:02Z

Title: Interaction of CCND2, CDKN1A, and POLD3 Variants in Mexican Patients with Colorectal Cancer Authors: Alvizo Rodríguez, Carlos Rogelio; Flores López, Beatriz Armida; Ayala Madrigal, María de la Luz; Partida Pérez, Miriam; Macías Gómez, Nelly Margarita; Peregrina Sandoval, Jorge; Suárez Villanueva, Alexis Sayuri; Moreno Ortiz, José Miguel; Cervantes Ortiz, Sergio; Maciel Gutiérrez, Víctor Manuel; Gutiérrez Angulo, Melva Abstract: ABSTRACT Background: Colorectal cancer is the second cause of death by cancer around the world. Sporadic colorectal cancer is the most frequent (75%), and it is produced by the interaction of environmental, epigenetic, and genetic factors. The accumulation of single-nucleotide variants in genes associated with cell proliferation, DNA repair, and/or apoptosis could confer a risk to cancer. The aim of this study was to analyze the gene–gene interactions among CCND2 (rs3217901), CDKN1A (rs1059234 and rs1801270), and POLD3 (rs3824999) variants in Mexican patients with colorectal cancer. Methods: We collected peripheral blood samples from 185 patients with sporadic colorectal cancer before treatment and from 185 unrelated blood donors as the reference group; all participants signed an informed consent form. DNA extraction was performed by Miller and Cetyltrimethylammonium bromide (CTAB)/ Dodecyltrimethylammonium bromide (DTAB) methods. Polymerase chain reaction– restriction fragment length polymorphism followed by polyacrylamide gel electrophoresis stained with AgNO3 methods were used to identify the variants rs3217901, rs1059234, rs1801270, and rs3824999. Odds ratio and single-nucleotide variant interaction were determined by single-locus analysis and Multifactorial Dimensionality Reduction software, respectively. Results: No association was found for CCND2 and CDKN1A variants; yet, a significant association for the GG genotype, G allele, and recessive and additive models for the POLD3 variant was observed (P < .05). The single-nucleotide variant–single-nucleotide variant interaction revealed the combination rs1059234, rs3217901, and rs3824999 as the best model and the comparison showed an increased risk (P < .05). Conclusion: Single-locus and gene–gene interaction analyses disclosed that both the rs3824999 (POLD3) variant and the combination of rs3217901 (CCND2), rs1059234 (CDKN1A), and rs3824999 (POLD3) genotypes increase the risk for colorectal cancer in Mexican population. Description: Artículo

Methylation analysis of MIR200 family in Mexican patients with colorectal cancer

2021-01-22T20:43:25Z

Title: Methylation analysis of MIR200 family in Mexican patients with colorectal cancer Authors: Alvizo Rodríguez, Carlos Rogelio; Ayala Madrigal, María de la Luz; Hernández Sandoval, Jesús Arturo; Ramirez Plascencia, Helen Haydee Fernanda; González Villaseñor, Christian Octavio; Macías Gómez, Nelly Margarita; Peregrina Sandoval, Jorge; Moreno Ortiz, José Miguel; Valenzuela Pérez, Jesús A.; Cruz Ramos, José Alfonso; Gutiérrez Angulo, Melva Abstract: The present study aimed to analyze the methylation pattern of the MIR200 family in the colorectal tissues and peripheral blood of colorectal cancer (CRC) patients. Previous informed consent, 102 samples of colorectal tissues (tumor and adjacent normal tissues) and 40 peripheral blood samples were collected from CRC patients. Additionally, we included a reference group of 40 blood samples. DNA extraction was done for colorectal tissues and peripheral blood. For methylation-specific PCR, we used bisulfite-treated DNA and controls for methylated and unmethylated DNA were included to each assay. PCR fragments were separated by 6% polyacrylamide gel electrophoresis. Methylation-positive and methylation-negative results were confirmed by bisulfite genomic sequencing technique. We analyzed 102 colorectal tissues and 40 blood samples from 51 CRC patients. MIR200B/MIR200A/MIR429 methylation analysis discloses no differences among tissues (p>0.05). However, MIR200C/MIR141 methylation showed differences between colorectal tissues and peripheral blood of CRC patients (p<0.0001) and mainly methylated alleles were observed in peripheral blood. These findings suggest a tissue-specific methylation pattern for the MIR200C/MIR141 promoter.

Association of the SLC6A4 gene 5HTTLPR polymorphism and ADHD with epilepsy, gestational diabetes, and parental substance abuse in Mexican mestizo children

2023-10-05T16:19:25Z

Title: Association of the SLC6A4 gene 5HTTLPR polymorphism and ADHD with epilepsy, gestational diabetes, and parental substance abuse in Mexican mestizo children Authors: Durán González, Jorge; Leal Ugarte, Evelia; Cruz Alcalá, Leonardo Eleazar; Gutiérrez Angulo, Melva; Gallegos Arreola, Martha Patricia; Meza Espinoza, Juan Pablo; Reyes Zurita, Itzayana; Padilla Macías, Patricia Lizbeth; Cruz Martín del Campo, Edgar Eleazar; Peralta Leal, Valeria Abstract: ABSTRACT Introduction. Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric conditions in childhood and a multifactorial condition attributable to genetic and/or environmental influence. Allelic variants in the serotonin transporter gene (SLC6A4) have been associated to lower transcriptional efficiency, changes in serotonin concentration in several brain regions, and ADHD development. Objective. To identify the association between the SLC6A4 alleles and ADHD diagnosis and risk factor phenotypes in children from a Mexican mestizo population. Method. In this study, 134 unrelated children were included and evaluated for ADHD, genotypification for the 5HTTLPR polymorphism, and identification of multiple phenotypes from their clinical records and family background for association analysis. Results. The following distribution of genotypes was observed: 23% SS, 49% SL, and 28% LL. From the phenotypes evaluated in the present study, gestational diabetes mellitus (p = .045), history of epilepsy (p = .047), and parental substance abuse (p = .033) showed an association with ADHD development in regression analysis along with the S variant. Discussion and conclusion. Results suggest that interaction of the S allele and some of the phenotypes analyzed may play a relevant role in the development of ADHD in the studied population. RESUMEN Introducción. El trastorno por déficit de atención e hiperactividad (TDAH) es uno de los padecimientos neuropsiquiátricos más comunes en la infancia. Como su naturaleza es multifactorial, es atribuible a influencias genéticas y/o ambientales. Las variantes alélicas del gen transportador de serotonina (SLC6A4) se han asociado previamente con cambios en los niveles de serotonina en algunas regiones cerebrales, así como con el desarrollo de TDAH. Objetivo. Identificar la posible asociación entre los alelos del gen SLC6A4 y el diagnóstico de TDAH, así como factores de riesgo en niños mestizos mexicanos. Método. En el presente estudio se incluyeron 134 niños, los cuales fueron evaluados para TDAH, genotipificación del polimorfismo 5HTTLPR e identificación de múltiples fenotipos en su historia clínica y antecedentes familiares para su análisis de asociación estadística. Resultados. Se mostró la siguiente distribución de genotipos: 23% SS, 49% SL y 28% LL. En un modelo de regresión, los fenotipos de diabetes mellitus gestacional (p = .045), historia de epilepsia (p = .047) y el abuso de sustancias de los padres (p = .033) mostraron asociación con la variante S y el desarrollo de TDAH. Discusión y conclusión. El presente estudio sugiere que el alelo S en conjunto con algunos fenotipos puede cumplir un papel importante en el desarrollo de TDAH en nuestra población.