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Congenital heart disease (CHD) can be complicated by pulmonary arterial hypertension (PAH). Cardiopulmonary bypass (CPB) for corrective surgery may cause endothelial dysfunction, involving endothelin-1 (ET-1), circulating endothelial cells (CECs), and endothelial progenitor cells (EPCs). These markers can gauge disease severity, but their levels in children's peripheral blood still lack consensus for prognostic value. The aim of our study was to investigate changes in ET-1, cytokines, and the absolute numbers (Æ) of CECs and EPCs in children 24 h before and 48 h after CPB surgery to identify high-risk patients of complications. A cohort of 56 children was included: 41 cases with CHD-PAH (22 with high pulmonary flow and 19 with low pulmonary flow) and 15 control cases. We observed that Æ-CECs increased in both CHD groups and that Æ-EPCs decreased in the immediate post-surgical period, and there was a strong negative correlation between ET-1 and CEC before surgery, along with significant changes in ET-1, IL8, IL6, and CEC levels. Our findings support the understanding of endothelial cell precursors' role in endogenous repair and contribute to knowledge about endothelial dysfunction in CHD.
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Puente Cardiopulmonar , Citocinas , Células Endoteliales , Células Progenitoras Endoteliales , Endotelina-1 , Cardiopatías Congénitas , Humanos , Endotelina-1/sangre , Endotelina-1/metabolismo , Células Progenitoras Endoteliales/metabolismo , Cardiopatías Congénitas/cirugía , Cardiopatías Congénitas/sangre , Cardiopatías Congénitas/metabolismo , Cardiopatías Congénitas/patología , Masculino , Femenino , Puente Cardiopulmonar/efectos adversos , Células Endoteliales/metabolismo , Citocinas/sangre , Citocinas/metabolismo , Niño , Preescolar , Lactante , Biomarcadores/sangre , Estudios de Casos y ControlesRESUMEN
Background: The distribution of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210 , and KMT2A-MLLT3 in the pediatric population with acute myeloid leukemia (AML) in many countries of Latin America is largely unknown. Therefore, we aimed to investigate the frequency of these fusion genes in children with de novo AML from Mexico City, which has one of the highest incidence rates of acute leukemia in the world. Additionally, we explored their impact in mortality during the first year of treatment. Methods: We retrospectively analyzed the presence of RUNX1-RUNXT1, PML-RARA, CBFB-MYH11, BCR-ABL1p210 , and KMT2A-MLLT3 by RT-PCR among 77 patients (<18 years) diagnosed with de novo AML between 2019 and 2021 in nine Mexico City hospitals. Results: The overall frequency of the fusion genes was 50.7%; RUNX1-RUNXT1 (22.1%) and PML-RARA (20.8%) were the most prevalent, followed by CBFB-MYH11 (5.2%) and BCR-ABL1p210 (2.4%). KMT2A-MLLT3 was not detected. Patients with PML-RARA showed the lowest survival with high early mortality events. However, more studies are required to evaluate the impact of analyzed fusion genes on the overall survival of the Mexican child population with AML. Conclusion: The pediatric population of Mexico City with AML had frequencies of AML1-ETO, PML-RARA, CBFB-MYH11, and BCR-ABL1p210 similar to those of other populations around the world. Patients with BCR-ABL1p210 and CBFB-MYH11 were few or did not die, while those with MLL-AF9 was not detected. Although patients with PML-RARA had a low survival and a high early mortality rate, further studies are needed to determine the long-term impacts of these fusion genes on this Latino population.
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Introduction: Over the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010-2017. Methods: The Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements. Results: A total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML. Conclusion: The ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors.
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Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Preescolar , Ciudades , Femenino , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/epidemiología , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p 190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.
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Background: Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The FLT3 gene participates in hematopoietic stem cell proliferation. FLT3 mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated. Aim of the study: This study aimed to identify the profile of FLT3 mutations in pediatric patients with de novo AML and to assess their possible influence on overall survival (OS) and other clinical features. Methods: Massive parallel target sequencing of FLT3 was performed in 80 patients. Results: FLT3 mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in FLT3 POS cases than in FLT3 NEG (p = 0.03). The average OS for FLT3 POS was 1.2 vs. 2.2 years in FLT3 NEG. There were no significant differences in the children's sex, age, percentage of blasts in bone marrow aspirate, or white blood cell count in peripheral blood at diagnosis between both groups. No differences were identified stratifying by the mutational load (high > 0.4) or type of mutation. The negative effect of FLT3 mutations was also observed in patients with acute promyelocytic leukemia (APL). Conclusions: FLT3 mutational profile is described in Mexican pediatric AML patients for the first time. Mutated FLT3 negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the FLT3 POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients.
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BACKGROUND: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL. METHODS: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes. RESULTS: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed. CONCLUSIONS: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.
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Obesidad Infantil/epidemiología , Obesidad Infantil/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Índice de Masa Corporal , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pronóstico , RecurrenciaRESUMEN
Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.
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Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética/genética , Adolescente , Adulto , Proteína de Unión a CREB/genética , Niño , Preescolar , Dineínas/genética , Femenino , Proteínas Activadoras de GTPasa/genética , Regulación Neoplásica de la Expresión Génica , Reordenamiento Génico , Humanos , Factor de Transcripción Ikaros/genética , Lactante , Masculino , México , Proteínas Nucleares/genética , Pronóstico , Proteínas Proto-Oncogénicas c-ets/genética , Proteínas de Unión a Caperuzas de ARN/genética , Proteínas de Unión al ARN/genética , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/genética , Adulto Joven , Proteína ETS de Variante de Translocación 6RESUMEN
The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Factores de Edad , Pesos y Medidas Corporales , Niño , Preescolar , Comorbilidad , Países en Desarrollo , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Desnutrición/diagnóstico , Desnutrición/epidemiología , México/epidemiología , Vigilancia de la Población , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prevalencia , Modelos de Riesgos Proporcionales , Inducción de Remisión , Factores SocioeconómicosRESUMEN
BACKGROUND: Mortality for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) is higher. In the end-stage renal disease (ESRD) the mortality is 20 times greater in comparison with general population. Natriuretic peptides, particularly type-B natriuretic peptide (BNP) have been studied as potential markers of risk of cardiovascular (CV) mortality. The aim of this paper is to determine whether BNP acts as a prognostic marker for CV mortality in patients with ESRD. METHODS: We studied 53 patients with ESRD prevalent in peritoneal dialysis without clinical evidence of heart failure at baseline was studied. The impact of variables was performed with linear regression model. The probability of survival was estimated by Kaplan-Meir analysis and the difference between survivals between groups with log-rank test according the levels of BNP. Adjusted hazard ratios were calculated with Cox proportional hazards analysis. RESULTS: BNP strongly predicts CVD mortality. The Cox regression model showed that BNP is a predictor of death from CVD. Patients with high levels of BNP were at increased risk of death. Several pathophysiological mechanisms not well defined are involved. CONCLUSIONS: BNP predicts CVD mortality in patients with ESRD. Serum measurement of this peptide can be useful for risk stratification in these patients and adjust treatment.
INTRODUCCIÓN: la mortalidad por enfermedad cardiovascular (ECV) en pacientes con enfermedad renal crónica (ERC) es alta. En la población con ERC terminal (ERCT) la mortalidad es hasta 20 veces mayor en comparación a la población general. Los péptidos natriuréticos, especialmente el péptido natriurético tipo-B (BNP), han sido estudiados como posibles marcadores de riesgo de mortalidad por ECV. El objetivo de este trabajo es determinar si el BNP actúa como un marcador pronóstico para mortalidad por ECV en pacientes con ERCT. MÉTODOS: se estudiaron 53 pacientes con ERCT prevalentes en diálisis peritoneal sin evidencia clínica de insuficiencia cardiaca al inicio del estudio. El impacto de las variables se realizó con el modelo de regresión lineal. La probabilidad de sobrevida fue estimada con el análisis de Kaplan-Meier y la diferencia entre grupos con el test de Log-Rank, acorde a los niveles de BNP dividido en tertiles. La asociación de riesgo fue calculada con el análisis proporcional de Cox ajustado. RESULTADOS: el BNP fuertemente predice la mortalidad por ECV. El modelo de regresión de Cox mostró que el BNP es un predictor de muerte por ECV. Pacientes con niveles altos de BNP tuvieron mayor riesgo de muerte. Varios mecanismos fisiopatológicos no bien definidos están involucrados. CONCLUSIONES: el BNP predice la mortalidad por ECV en pacientes con ERCT. La medición sérica de este péptido puede ser útil para la estratificación de riesgo en estos pacientes y ajustar el plan terapéutico
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INTRODUCTION: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease. AIMS: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions. MATERIAL AND METHODS: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated. RESULTS: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively. CONCLUSIONS: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.
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Leucemia Mieloide Aguda/epidemiología , Adolescente , Niño , Ciudades/epidemiología , Humanos , Incidencia , Lactante , Leucemia Mieloide Aguda/etiología , Masculino , México/epidemiología , Factores de Riesgo , Distribución por SexoRESUMEN
Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010-2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.
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Reordenamiento Génico , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Células HL-60 , Humanos , México/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prevalencia , Tasa de SupervivenciaRESUMEN
Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.
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Inestabilidad Cromosómica , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/fisiopatología , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Ensayo Cometa , Estudios Transversales , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Femenino , Productos Finales de Glicación Avanzada/sangre , Humanos , Inflamación , Interleucina-6/sangre , Modelos Logísticos , Linfocitos/patología , Masculino , Malondialdehído/sangre , Pruebas de Micronúcleos , Persona de Mediana Edad , Estrés Oxidativo , Insuficiencia Renal Crónica/genética , Albúmina Sérica/análisis , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
TP53 is the most commonly mutated gene in human cancers. Approximately 90% of mutations in this gene are localized between domains encoding exons 5 to 8. The aim of this investigation was to examine the ability of the low density DNA microarray with the assistance of double tandem hybridization platform to characterize TP53 mutational hotspots in exons 5, 7, and 8 of the TP53. Nineteen capture probes specific to each potential mutation site were designed to hybridize to specific site. Virtual hybridization was used to predict the stability of hybridization of each capture probe with the target. Thirty-three DNA samples from different sources were analyzed for mutants in these exons. A total of 32 codon substitutions were found by DNA sequencing. 24 of them a showed a perfect correlation with the hybridization pattern system and DNA sequencing analysis of the regions scanned. Although in this work we directed our attention to some of the most representative mutations of the TP53 gene, the results suggest that this microarray system proved to be a rapid, reliable, and effective method for screening all the mutations in TP53 gene.
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In the modern society, cancer remains an important cause of death. Cancer development is a very complex process that involves alterations in genes regulating cellular growth. Among these alterations or variations, are included point mutations, genetic susceptibility by single nucleotide polymorphisms or "SNP" and alteration or loss in tumor suppressor genes functions. The tumor suppressor TP53 is one of the most important and studied genes on cancer genetics. Therefore, it has been demonstrated that TP53 present mutations in more than 50% of all types of human cancer and encodes a multifunctional protein whose absence contributes to genomic instability, the accumulation of mutations and increased tumor development. The identification of such alterations in cancerous cells at level of single nucleotide is very important, because its implication in the loss or alteration in the function of this gene, its clinical relevance and finally, its association with response to therapy and prognosis. Due to the large interesting issue, in this work we are focused only in two of the most common genetic variations present in this gene: the point mutations and SNP remarking some outstanding molecular characteristics needed for design its analysis.
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Genes p53 , Cocarcinogénesis , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Inestabilidad Genómica , Humanos , Pérdida de Heterocigocidad , Mutación Missense , Síndromes Neoplásicos Hereditarios/genética , Mutación Puntual , Polimorfismo de Nucleótido Simple , Estructura Terciaria de Proteína , Proteína p53 Supresora de Tumor/química , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/fisiologíaRESUMEN
In the modern society, cancer remains an important cause of death. Cancer development is a very complex process that involves alterations in genes regulating cellular growth. Among these alterations or variations, are included point mutations, genetic susceptibility by single nucleotide polymorphisms or "SNP" and alteration or loss in tumor suppressor genes functions. The tumor suppressor TP53 is one of the most important and studied genes on cancer genetics. Therefore, it has been demonstrated that TP53 present mutations in more than 50% of all types of human cancer and encodes a multifunctional protein whose absence contributes to genomic instability, the accumulation of mutations and increased tumor development. The identification of such alterations in cancerous cells at level of single nucleotide is very important, because its implication in the loss or alteration in the function of this gene, its clinical relevance and finally, its association with response to therapy and prognosis. Due to the large interesting issue, in this work we are focused only in two of the most common genetic variations present in this gene: the point mutations and SNP remarking some outstanding molecular characteristics needed for design its analysis.
El cáncer continúa siendo una importante causa de muerte en la sociedad moderna. Los procesos en el desarrollo del cáncer son muy complejos e involucran alteraciones en genes implicados en la proliferación celular. Entre estas alteraciones o variaciones genéticas se incluyen las mutaciones puntuales, la susceptibilidad genética por polimorfismos de un solo nucleótido o "SNP", así como la pérdida o alteración en la función de genes supresores de tumores. El gen supresor de tumores TP53 es uno de los genes más importantes y estudiados en la genética del cáncer, ya que se encuentra mutado en más del 50% de todos los tipos de cáncer humano y codifica para una proteína multifuncional cuya deficiencia contribuye a la inestabilidad genómica que conduce a la acumulación de mutaciones y a la aceleración en el desarrollo del tumor. Es importante el estudio de dichas alteraciones genéticas presentes en las células cancerosas que puedan ser detectadas a nivel de un solo nucleótido, por su implicación en la pérdida o alteración en la función del gen TP53, así como por la relevancia clínica que ellas puedan tener al ser asociadas a la respuesta de una terapia particular o al pronóstico. Debido a la extensión de este trabajo solamente revisaremos dos de las variaciones genéticas importantes en este gen: las mutaciones puntuales y los SNP, haciendo ánfasis en algunas características moleculares que son relevantes en el diseño de estrategias de análisis para su detección.