PAZ Y MIÑO CEPEDA, CÉSAR ANTONIO

Preferred name

Main Affiliation

Facultad de Ciencias de la Salud Eugenio Espejo

ORCID

0000-0002-6693-7344

Scopus Author ID

57196263036

Now showing 1 - 10 of 49

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Ancestry study in Ecuadorian population with multiple myeloma
(Ovid Technologies (Wolters Kluwer Health), 2017)
P.E. Leone
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A. Cabrera-Andrade
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J.M. García-Cárdenas
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D.A. González
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GUEVARA RAMIREZ, ALEXANDRA PATRICIA
Scopus© Citations 1
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A deep analysis using panel-based next-generation sequencing in an Ecuadorian pediatric patient with anaplastic astrocytoma: a case report
(Springer Science and Business Media LLC, 2020-08-31)
Jennyfer M. García-Cárdenas
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ZAMBRANO ESPINOSA, ANA KARINA
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Gabriel Runruil
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GUEVARA RAMIREZ, ALEXANDRA PATRICIA
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Santiago Guerrero
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Anaplastic astrocytoma is a rare disorder in children from 10 to 14 years of age, with an estimated 0.38 new cases per 100,000 people per year worldwide. Panel-based next-generation sequencing opens new possibilities for diagnosis and therapy of rare diseases such as this one. Because it has never been genetically studied in the Ecuadorian population, we chose to genetically characterize an Ecuadorian pediatric patient with anaplastic astrocytoma for the first time. Doing so allows us to provide new insights into anaplastic astrocytoma diagnosis and treatment.</jats:p></jats:sec><jats:sec><jats:title>Case presentation</jats:title><jats:p>Our patient was a 13-year-old Mestizo girl with an extensive family history of cancer who was diagnosed with anaplastic astrocytoma. According to ClinVar, SIFT, and PolyPhen, the patient harbored 354 genomic alterations in 100 genes. These variants were mostly implicated in deoxyribonucleic acid (DNA) repair. The top five most altered genes were<jats:italic>FANCD2</jats:italic>,<jats:italic>NF1</jats:italic>,<jats:italic>FANCA</jats:italic>,<jats:italic>FANCI</jats:italic>, and<jats:italic>WRN.</jats:italic>Even though<jats:italic>TP53</jats:italic>presented only five mutations, the rs11540652 single-nucleotide polymorphism classified as pathogenic was found in the patient and her relatives; interestingly, several reports have related it to Li-Fraumeni syndrome. Furthermore,<jats:italic>in silico</jats:italic>analysis using the Open Targets Platform revealed two clinical trials for pediatric anaplastic astrocytoma (studying cabozantinib, ribociclib, and everolimus) and 118 drugs that target the patient’s variants, but the studies were not designed specifically to treat pediatric anaplastic astrocytoma.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Next-generation sequencing allows genomic characterization of rare diseases; for instance, this study unraveled a pathogenic single-nucleotide polymorphism related to Li-Fraumeni syndrome and identified possible new drugs that specifically target the patient’s variants. Molecular tools should be implemented in routine clinical practice for early detection and effective preemptive intervention delivery and treatment.</jats:p></jats:sec>
Scopus© Citations 2
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OncoOmics approaches to reveal essential genes in breast cancer: a panoramic view from pathogenesis to precision medicine
(Springer Science and Business Media LLC, 2020-03-24)
Andrés López-Cortés
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PAZ Y MIÑO CEPEDA, CESAR ANTONIO
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Santiago Guerrero
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Alejandro Cabrera-Andrade
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Stephen J. Barigye
<jats:title>Abstract</jats:title><jats:p>Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. <jats:italic>RAC1</jats:italic>, <jats:italic>AKT1</jats:italic>, <jats:italic>CCND1</jats:italic>, <jats:italic>PIK3CA</jats:italic>, <jats:italic>ERBB2</jats:italic>, <jats:italic>CDH1</jats:italic>, <jats:italic>MAPK14</jats:italic>, <jats:italic>TP53</jats:italic>, <jats:italic>MAPK1</jats:italic>, <jats:italic>SRC</jats:italic>, <jats:italic>RAC3</jats:italic>, <jats:italic>BCL2</jats:italic>, <jats:italic>CTNNB1</jats:italic>, <jats:italic>EGFR</jats:italic>, <jats:italic>CDK2</jats:italic>, <jats:italic>GRB2</jats:italic>, <jats:italic>MED1</jats:italic> and <jats:italic>GATA3</jats:italic> were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.</jats:p>
Scopus© Citations 47
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Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis
(Frontiers Media SA, 2020-10-26)
Verónica Yumiceba
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Andrés López-Cortés
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Andy Pérez-Villa
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Iván Yumiseba
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Santiago Guerrero
<jats:p>Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. Epidemiological findings revealed that women with PCOS are prone to develop certain cancer types due to their shared metabolic and endocrine abnormalities. However, the mechanism that relates PCOS and oncogenesis has not been addressed. Herein, in this review article the genomic status, transcriptional and protein profiles of 264 strongly PCOS related genes (PRG) were evaluated in endometrial cancer (EC), ovarian cancer (OV) and breast cancer (BC) exploring oncogenic databases. The genomic alterations of PRG were significantly higher when compared with a set of non-diseases genes in all cancer types.<jats:italic>PTEN</jats:italic>had the highest number of mutations in EC,<jats:italic>TP53</jats:italic>, in OC, and<jats:italic>FSHR</jats:italic>, in BC. Based on clinical data, women older than 50 years and Black or African American females carried the highest ratio of genomic alterations among all cancer types. The most altered signaling pathways were p53 in EC and OC, while Fc epsilon RI in BC. After evaluating PRG in normal and cancer tissue, downregulation of the differentially expressed genes was a common feature. Less than 30 proteins were up and downregulated in all cancer contexts. We identified 36 highly altered genes, among them 10 were shared between the three cancer types analyzed, which are involved in the cell proliferation regulation, response to hormone and to endogenous stimulus. Despite limited PCOS pharmacogenomics studies, 10 SNPs are reported to be associated with drug response. All were missense mutations, except for rs8111699, an intronic variant characterized as a regulatory element and presumably binding site for transcription factors. In conclusion,<jats:italic>in silico</jats:italic>analysis revealed key genes that might participate in PCOS and oncogenesis, which could aid in early cancer diagnosis. Pharmacogenomics efforts have implicated SNPs in drug response, yet still remain to be found.</jats:p>
Scopus© Citations 33
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Understanding Celiac Disease From Genetics to the Future Diagnostic Strategies
(SAGE Publications, 2017-01-01)
Carolina Salazar
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Jennyfer M García-Cárdenas
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PAZ Y MIÑO CEPEDA, CESAR ANTONIO
<jats:p> Celiac disease (CD) is an autoimmune disorder characterized by the permanent inflammation of the small bowel, triggered by the ingestion of gluten. It is associated with a number of symptoms, the most common being gastrointestinal. The prevalence of this illness worldwide is 1%. One of the main problems of CD is its difficulty to be diagnosed due to the various presentations of the disease. Besides, in many cases, CD is asymptomatic. Celiac disease is a multifactorial disease, HLA-DQ2 and HLA-DQ8 haplotypes are predisposition factors. Nowadays, molecular markers are being studied as diagnostic tools. In this review, we explore CD from its basic concept, manifestations, types, current and future methods of diagnosis, and associated disorders. Before addressing the therapeutic approaches, we also provide a brief overview of CD genetics and treatment. </jats:p>
Scopus© Citations 16
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Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis
(Springer Science and Business Media LLC, 2017-08-08)
Eduardo Tejera
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Maykel Cruz-Monteagudo
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Germán Burgos
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María-Eugenia Sánchez
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Aminael Sánchez-Rodríguez
Scopus© Citations 22
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TCGA Pan-Cancer Genomic Analysis of Alternative Lengthening of Telomeres (ALT) Related Genes
(MDPI AG, 2020-07-21)
Isaac Armendáriz-Castillo
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Andrés López-Cortés
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Jennyfer García-Cárdenas
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GUEVARA RAMIREZ, ALEXANDRA PATRICIA
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Paola E. Leone
<jats:p>Telomere maintenance mechanisms (TMM) are used by cancer cells to avoid apoptosis, 85–90% reactivate telomerase, while 10–15% use the alternative lengthening of telomeres (ALT). Due to anti-telomerase-based treatments, some tumors switch from a telomerase-dependent mechanism to ALT; in fact, the co-existence between both mechanisms has been observed in some cancers. Although different elements in the ALT pathway are uncovered, some molecular mechanisms are still poorly understood. Therefore, with the aim to identify potential molecular markers for the study of ALT, we combined in silico approaches in a 411 telomere maintenance gene set. As a consequence, we conducted a genomic analysis of these genes in 31 Pan-Cancer Atlas studies from The Cancer Genome Atlas and found 325,936 genomic alterations; from which, we identified 20 genes highly mutated in the cancer studies. Finally, we made a protein-protein interaction network and enrichment analysis to observe the main pathways of these genes and discuss their role in ALT-related processes, like homologous recombination and homology directed repair. Overall, due to the lack of understanding of the molecular mechanisms of ALT cancers, we proposed a group of genes, which after ex vivo validations, could represent new potential therapeutic markers in the study of ALT.</jats:p>
Scopus© Citations 13
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Genetic variation of high-altitude Ecuadorian population using autosomal STR markers
(Elsevier BV, 2019-12)
ZAMBRANO ESPINOSA, ANA KARINA
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A. Gaviria
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M. Vela
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C. Rodríguez-Pollit
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GUEVARA RAMIREZ, ALEXANDRA PATRICIA
Scopus© Citations 1
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Clinical, cytogenetic, and molecular findings in a patient with ring chromosome 4: case report and literature review
(Springer Science and Business Media LLC, 2019-11-21)
PAZ Y MIÑO CEPEDA, CESAR ANTONIO
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Ana Proaño
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Stella D. Verdezoto
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Juan Luis García
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Jesús María Hernández-Rivas
<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Since 1969, 49 cases have been presented on ring chromosome 4. All of these cases have been characterized for the loss of genetic material. The genes located in these chromosomal regions are related to the phenotype.</jats:p> </jats:sec><jats:sec> <jats:title>Case presentation</jats:title> <jats:p>A 10-year-old Ecuadorian Mestizo girl with ring chromosome 4 was clinically, cytogenetically and molecularly analysed. Clinical examination revealed congenital anomalies, including microcephaly, prominent nose, micrognathia, low set ears, bilateral clinodactyly of the fifth finger, small sacrococcygeal dimple, short stature and mental retardation. Cytogenetic studies showed a mosaic karyotype, mos 46,XX,r(4)(p16.3q35.2)/46,XX, with a ring chromosome 4 from 75 to 79% in three studies conducted over ten years. These results were confirmed by fluorescence in situ hybridization (FISH). Loss of 1.7 Mb and gain of 342 kb in 4p16.3 and loss of 3 Mb in 4q35.2 were identified by high-resolution mapping array.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Most cases with ring chromosome 4 have deletion of genetic material in terminal regions; however, our case has inv dup del rearrangement in the ring chromosome formation. Heterogeneous clinical features in all cases reviewed are related to the amount of genetic material lost or gained. The application of several techniques can increase our knowledge of ring chromosome 4 and its deviations from typical “ring syndrome.”</jats:p> </jats:sec>
Scopus© Citations 2
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Tracing the genetic history of the ‘Cañaris’ from Ecuador and Peru using uniparental DNA markers
(Springer Science and Business Media LLC, 2020-09)
José R. Sandoval
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Daniela R. Lacerda
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Marilza M. S. Jota
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Paulo Robles-Ruiz
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Pierina Danos
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>According to history, in the pre-Hispanic period, during the conquest and Inka expansion in Ecuador, many Andean families of the Cañar region would have been displaced to several places of<jats:italic>Tawantinsuyu</jats:italic>, including Kañaris, a Quechua-speaking community located at the highlands of the Province of Ferreñafe, Lambayeque (Peru). Other families were probably taken from the Central Andes to a place close to Kañaris, named Inkawasi. Evidence of this migration comes from the presence near the Kañaris–Inkawasi communities of a village, a former Inka camp, which persists until the present day. This scenario could explain these toponyms, but it is still controversial. To clarify this historical question, the study presented here focused on the inference of the genetic relationship between ‘Cañaris’ populations, particularly of Cañar and Ferreñafe, compared to other highland populations. We analysed native patrilineal Y chromosome haplotypes composed of 15 short tandem repeats, a set of SNPs, and maternal mitochondrial DNA haplotypes of control region sequences.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After the genetic comparisons of local populations—three from Ecuador and seven from Peru—, Y chromosome analyses (<jats:italic>n</jats:italic> = 376) indicated that individuals from the Cañar region do not share Y haplotypes with the Kañaris, or even with those of the Inkawasi. However, some Y haplotypes of Ecuadorian ‘Cañaris’ were associated with haplotypes of the Peruvian populations of Cajamarca, Chivay (Arequipa), Cusco and Lake Titicaca, an observation that is congruent with colonial records. Within the Kañaris and Inkawasi communities there are at least five clans in which several individuals share haplotypes, indicating that they have recent common ancestors. Despite their relative isolation, most individuals of both communities are related to those of the Cajamarca and Chachapoyas in Peru, consistent with the spoken Quechua and their geographic proximity. With respect to mitochondrial DNA haplotypes (<jats:italic>n</jats:italic> = 379), with the exception of a shared haplotype of the D1 lineage between the Cañar and Kañaris, there are no genetic affinities.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Although there is no close genetic relationship between the Peruvian Kañaris (including Inkawasi) and Ecuadorian Cañar populations, our results showed some congruence with historical records.</jats:p></jats:sec>
Scopus© Citations 7

PAZ Y MIÑO CEPEDA, CÉSAR ANTONIO

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