Unraveling the genomic landscape of Campylorhynchus wrens along western Ecuador's precipitation gradient: Insights into hybridization, isolation by distance, and isolation by the environment.

Environmental gradients have the potential to influence genetic differentiation among populations ultimately leading to allopatric speciation. However, environmental gradients can also facilitate hybridization between closely related taxa. We investigated a putative hybrid zone in western Ecuador, involving two polytypic wren species (Aves: Troglodytidae), Campylorhynchus zonatus and C. fasciatus. Our study addressed two primary questions: (1) Is there evidence of population structure and genetic admixture between these taxa in western Ecuador? and (2) What are the relative contributions of isolation by distance and isolation by the environment to the observed genetic differentiation along the environmental gradient in this region? We analyzed 4409 single-nucleotide polymorphisms (SNPs) from 112 blood samples sequenced using ddRadSeq and a de novo assembly. The optimum number of genetic clusters ranged from 2 to 4, aligning with geographic origins, known phylogenetics, and physical or ecological constraints. We observed notable transitions in admixture proportions along the environmental gradient in western Ecuador between C. z. brevirostris and the northern and southern genetic clusters of C. f. pallescens. Genetic differentiation between the two C. f. pallescens populations could be attributed to an unreported potential physical barrier in central western Ecuador, where the proximity of the Andes to the coastline restricts lowland habitats, limiting dispersal and gene flow, especially among dry-habitat specialists. The observed admixture in C. f. pallescens suggests that this subspecies may be a hybrid between C. z. brevirostris and C. fasciatus, with varying degrees of admixture in western Ecuador and northwestern Peru. We found evidence of isolation by distance, while isolation by the environment was less pronounced but still significant for annual mean precipitation and precipitation seasonality. This study enhances our understanding of avian population genomics in tropical regions.

A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9-12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer.

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9-12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9-12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT-qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9-12 alleles using nanopore long-sequencing. Using the Kruskal-Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9-12 and identifying which of them has developed cancer.

SARS-CoV-2 seroprevalence and respiratory disease disability claims in Mexico City Metropolitan Area.

OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.

Prevalence of SARS-CoV-2 antibodies in cancer patients and healthcare workers vaccinated with two doses of BNT162b2 or AZD122. A propensity analysis.

BACKGROUND: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. OBJECTIVES: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. MATERIAL AND METHODS: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. RESULTS: One-hundred and twenty-seven CPs (22%) and 439 HCWs (78%) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. CONCLUSIONS: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.

ANTECEDENTES: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). OBJETIVOS: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. MATERIAL Y MÉTODOS: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. RESULTADOS: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. CONCLUSIONES: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.

Prevalencia de anticuerpos contra SARS-CoV-2 en pacientes con cáncer y trabajadores de la salud vacunados con dos dosis de BNT162b2 o AZD122. Análisis de propensión / Prevalence of SARS-CoV-2 antibodies in cancer patients and healthcare workers vaccinated with two doses of BNT162b2 or AZD122. A propensity analysis

Resumen Antecedentes: La vacunación es la intervención más efectiva para reducir la carga de enfermedad por SARS-CoV-2; sin embargo, persisten brechas en el conocimiento en relación con la respuesta inmunológica de los pacientes con cáncer (PC). Objetivos: Evaluar la respuesta humoral (anticuerpos anti-S) en PC y trabajadores de salud (TS) vacunados con dos dosis de la vacuna BNT162b2 o AZD122. Material y métodos: Se cuantificaron anticuerpos poliespecíficos contra la proteína de espiga de SARS-CoV-2 (anti-S) y se efectuó una puntuación de propensión 1:1 para equilibrar las características basales. Se realizaron regresiones logísticas múltiples para evaluar el efecto de las variables relacionadas con la respuesta humoral. Resultados: Se incluyeron 127 PC (22 %) y 439 TS (78 %). Ambas poblaciones desarrollaron anticuerpos anti-S en respuesta a la vacunación. La vacuna de ARNm (BNT162b2) se asoció a mayor probabilidad de mostrar concentraciones de anticuerpos anti-S ≥ 1000 UI/mL, mientras que el cáncer activo se relacionó con menor probabilidad de presentar títulos altos de anticuerpos. Conclusiones: La vacuna BNT162b2 se asoció a respuesta humoral mayor. Es necesario contar con más información y estrategias de vacunación en pacientes inmunosuprimidos. Es relevante la selección de los mejores biológicos para esta población y considerar las características individuales.

Abstract Background: Vaccination is the most effective intervention for reducing the burden of SARS-CoV-2-related disease; however, gaps in knowledge regarding cancer patients (CPs) immune response persist. Objectives: To evaluate the humoral response (anti-S antibodies) in CPs and healthcare workers (HCWs) vaccinated with two doses of BNT162b2 or AZD122 vaccines. Material and methods: Polyspecific anti-SARS-CoV-2 spike protein (anti-S) antibodies were quantified, and a 1:1 propensity score was used to balance baseline characteristics. Multiple logistic regressions were carried out to evaluate the effect of humoral response-related variables. Results: One-hundred and twenty-seven CPs (22 %) and 439 HCWs (78 %) were included. Both populations developed anti-S antibodies in response to vaccination. The mRNA-based vaccine (BNT162b2) was associated with higher odds of having anti-S antibody titers ≥ 1,000 U/mL, while active cancer was related to a lower probability of developing high antibody titers. Conclusions: The BNT162b2 vaccine was associated with a higher humoral response. It is necessary for more information and vaccination strategies to be available for immunosuppressed patients in order to select the best biologics for this population based on individual characteristics.

A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.

Cancer Prevention Behaviors in Workers of a Referral Cancer Center in Mexico City: A Pilot Study on Early Detection Awareness for Cancer.

BACKGROUND: Prevention strategies for cancer are necessary. Health workers who often serve as role models bear responsibility for prevention counseling and programs. However, whether their habits and behaviors reflect prevention goals are unknown. We describe the prevalence of cancer risk factors and prevention behaviors in health workers of a referral cancer center in Mexico City. METHODS: Cross-sectional study in which workers of the National Cancer Institute were invited to participate in a prevention program, risk factor survey, and nutrition, psychological, and genetic counseling were included. The likelihood of cancer was calculated based on the presence of risk factors. Factors associated with prevention behaviors were identified by logistic regression. RESULTS: We recruited 301 workers; 77% were women. The median self-reported BMI was 26.4 kg/m2, 9.97% smoked, 78% drank alcohol, and 89% did not get at least 150 min/week of physical activity. In women, age (OR = 1.3 95%CI 1.01-1.06) and physical activity of 150 min/week (OR = 2.52 95% CI 1.28-4.96) were associated with cancer prevention behaviors. No risk factors were associated with healthy behaviors among men. CONCLUSION: Health workers may have unhealthy lifestyles and behaviors, is essential to create supportive environments to promote cancer prevention counseling and programs effectively.

Trastornos psiquiátricos posteriores al diagnóstico oncológico de primera vez: Revisión sistemática / Psychiatric disorders after first-time cancer diagno-sis: A systematic review

Introducción: Los pacientes oncológicos tienen un mayor riesgo de desarrollar signos, síntomas y trastornos psiquiátricos y suicidio. El objetivo de la presente revisión sistemática fue recopilar evidencia respecto de los trastornos psiquiátricos posteriores al primer diagnóstico oncológico, para obtener información de calidad sobre su frecuencia, impacto en el paciente y tratamiento en el mundo. Metodología: Revisión sistemática de la literatura publicada desde enero de 2016 hasta marzo de 2021. Las fuentes de información fueron artículos de revistas indexadas en bases de datos, como Pubmed, Wiley Online Library, y Google académico. Se incluyeron artículos científicos sobre trastornos psiquiátricos después del diagnóstico oncológico; desde 2016 hasta marzo de 2021; en idioma castellano o inglés, originales, con diseño observacional, analítico, prospectivo, retrospectivo, transversal, de series de casos, revisiones sistemáticas y metaanálisis, con un nivel de calidad de la evidencia según el sistema GRADE "Alto y Moderado" y un grado de cumplimento de CONSORT, PRISMA-p, o STROBE ≥ 75 %. Resultados: Se incluyeron 19 artículos; con una población total de 6 377 483 pacientes adultos. Dentro de los trastornos mentales más frecuentes se encontraron ansiedad (1.8 %-78.8 %); depresión (4.2 %- 61.1 %) y estrés (1.9 %-56.1 %). La aparición de estos trastornos se relacionó con mayor sintomatología y peor pronóstico, aumentando las visitas al hospital y con esto mayor mortalidad (P < 0.05). El abordaje psicoterapéutico debe ser personalizado, enfocado en fortalecer la resiliencia, autoestima, afrontamiento y resolución de crisis. Conclusión: Los trastornos psiquiátricos después del primer diagnóstico oncológico son frecuentes, tienen un impacto negativo en el pronóstico y calidad de vida de los pacientes, por lo que es necesario un diagnóstico y tratamiento oportuno, mediante un esquema psicoterapéutico personalizado a cada paciente.

Introduction: Cancer patients are at increased risk of developing signs, symptoms, psychiatric disorders, and suicide. The objective of this systematic review was to collect evidence regarding psychiatric disorders after the first oncological diagnosis and obtain quality information on their frequency, impact on the patient, and treatment in the world. Methodology: Systematic review of the literature published from January 2016 to March 2021. The sources of information were articles from journals indexed in databases, such as PubMed, Wiley Online Library, and Google Scholar. Scientific papers on psychiatric disorders after cancer diagnosis were included; from 2016 to March 2021; in Spanish or English, original, with an observational, analytical, prospective, retrospective, cross-sectional, case series, systematic review, and meta-analysis de-sign, with a level of quality of evidence according to the GRADE system "High and Moderate" and a grade of compliance with CONSORT, PRISMA-p, or STROBE ≥ 75%. Results: Nineteen articles were included, with a total population of 6,377,483 adult patients. Among the most frequent mental disorders were anxiety (1.8%-78.8%), depression (4.2%-61.1%), and stress (1.9%-56.1%). The appearance of these disorders was related to more significant symptoms and worse prognosis, increased hospital visits, and higher mortality (P < 0.05). The psychotherapeutic approach must be personalized and strengthen resilience, self-esteem, coping, and crisis resolution. Conclusion: Psychiatric disorders after the first oncological diagnosis are frequent; they hurt patients' prognosis and quality of life. Timely diagnosis and treatment are necessary through a personalized psychotherapeutic scheme for each patient.

Lead exposure does not affect baseline and induced innate immunity in quails.

Lead (Pb) is one of the most common metals found in ecosystems in elevated concentrations derived mainly from anthropogenic activities. Pb toxicity is of special concern in birds due to its capacity for bioaccumulation in the liver, bones, and kidneys causing physiological disruptions. Such disruptions can be lethal in a few days after Pb acute intoxication and they are associated with several million deaths of birds. Moreover, Pb may work as an immunosuppressant as it affects the cell-mediated and humoral immune responses, including components of the acute-phase response (APR). We (1) examined the effects of Pb contamination on the innate immune system, body mass, and food intake of Japanese quails (Coturnix coturnix japonica), and (2) evaluated the effects of Pb on its APR after exposing the animals to Pb acetate in drinkable water during 7 days. We found that Pb contamination increased the number of circulating white blood cells (WBCs), but no effect was found on body mass, food intake, the heterophil/lymphocyte (H/L) ratio, and haptoglobin (Hp) concentration. When Pb-exposed birds were injected with lipopolysaccharide from Escherichia coli to activate the APR, they had a negative body mass ratio, reduced food intake, and increased the number of WBCs, the H/L ratio, and the Hp concentration. We conclude that Pb exposure at this dose did not affect baseline values of the constitutive response and that it did not affect the APR of quails, but commend for further studies testing the effect of different Pb doses.

microRNA Profile Associated with Positive Lymph Node Metastasis in Early-Stage Cervical Cancer.

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients-one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.

SARS-CoV-2 Infection Rate in Patients With Cancer and Health Care Workers in a Chemoradiotherapy Unit During the Pandemic: A Prospective Cohort in Mexico.

PURPOSE: Cancer treatment during the COVID-19 pandemic represents a challenge. Hospital visits to receive treatment and interaction with health care workers (HCW) represent potential contagious events. We aimed to determine SARS-CoV-2 infection rate among patients with cancer and HCW of a chemoradiotherapy unit localized in a center designated as a COVID-19 priority facility in Mexico City. We also determined the diagnostic performance of a clinical questionnaire (CQ) as a screening tool and anti-SARS-CoV-2 antibody seroconversion rate. METHODS: HCW and patients with solid tumors attending the chemoradiotherapy unit signed informed consent. To determine SARS-CoV-2 infection rate prospectively, a nasopharyngeal swab for SARS-CoV-2 real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was performed every 2 weeks in asymptomatics. An electronic CQ interrogating COVID-19-related symptoms was sent daily. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were measured at baseline and at the end of the study period. RESULTS: From June to September 2020, we included 130 asymptomatic participants, 44.6% HCW and 55.4% patients with cancer. During a median follow-up of 85 days, 634 nasopharyngeal swabs were performed. Average SARS-CoV-2 monthly incidence was 4.6% (3.15%-7.47%), and cumulative infection rate was 13.8% (18 of 130). Cases were mostly asymptomatic (66%), and no hospitalizations or deaths were recorded. The CQ as a screening tool provided a sensitivity of 27.7%, a positive predictive value of 26.3%, and a positive likelihood ratio of 12. SARS-CoV-2 IgG seroconversion rate was 27.7% among those with a positive RT-PCR. CONCLUSION: Patients with cancer on treatment can have uncomplicated COVID-19 outcomes. Biweekly RT-qPCR testing detects asymptomatic infections, prevents transmission, and should be implemented in units to increase patient safety. CQ increase RT-qPCR diagnostic yield and may prioritize testing in resource-deprived settings. Post-infection IgG seroconversion is unreliable.

[Isomorfismo cardiaco: Una perspectiva multidisciplinaria]. / Atrial isomerism: A multidisciplinary perspective

Atrial isomerism describes complex anatomical findings with defects in the determination of lateralization; being a rare situation, with a prevalence of 1 in every 10.000 to 20.000 live births, with an incidence of up to 4% of all cardiac malformations. The diagnosis can be made in the neonatal age; however, clinical presentation is nonspecific. Depending on the spectrum of malformations, complex and invasive diagnostic tools may be required. Treatment is varied and can range from palliative surgery in view of univentricular physiology to total correction surgery for biventricular repair.

El isomorfismo cardiaco describe hallazgos anatómicos complejos con defectos en la determinación de la lateralización. Es una situación poco frecuente, con prevalencia de 1 en cada 10,000 a 20,000 nacidos vivos, con incidencia hasta del 4% de todas las malformaciones cardiacas. El diagnóstico puede realizarse en la etapa neonatal; sin embargo, el cuadro clínico es inespecífico. De acuerdo con el espectro de malformaciones se pueden necesitar medios diagnósticos complejos e invasivos. El tratamiento es variado y puede ir desde la cirugía paliativa en vista de una fisiología univentricular hasta una cirugía de corrección total para una reparación biventricular.

SARS-CoV-2 positivity rates in asymptomatic workers at a cancer referral center in Mexico City: A prospective observational study in the context of adapting hospitals back to regular practice.

BACKGROUND: Healthcare workers are at increased risk of SARS-CoV-2 infection. The positivity rates in hospitals that do not receive patients with COVID-19, such as the National Cancer Institute (INCan) in Mexico, and the associated factors are unknown. OBJECTIVE: To assess the incidence and factors associated with SARS-CoV-2 infection in health workers at INCan. METHODS: A cohort study of 531 workers who were followed for 6 months. RT-PCR analysis of saliva and nasopharyngeal swab samples were used in the baseline and to confirm cases during follow-up The incidence rate ratio was calculated according to the measured characteristics and the associated factors were calculated using logistic regression models. RESULTS: Out of 531 workers, 9.6% tested positive for SARS-CoV-2, Being male (RR: 2.07, 95% CI: 1.1-3.8, P = .02), performing administrative tasks (RR: 1.99, 95% CI: 1.0-3.9, P = .04), and having relatives also working at INCan (RR: 3.7, 95% CI: 1.4-9.5, P < .01) were associated with higher positivity rates. DISCUSSION: Incidence of positive cases in health workers were similar to that reported in non-COVID hospitals from other countries. CONCLUSIONS: Even though active surveillance helped to detect a significant number of asymptomatic infections, it is still necessary to reinforce preventive measures in non-medical staff to prevent nosocomial transmission.

Emergence and spread of the potential variant of interest (VOI) B.1.1.519 of SARS-CoV-2 predominantly present in Mexico.

SARS-CoV-2 variants emerged in late 2020, and at least three variants of concern (B.1.1.7, B.1.351, and P1) have been reported by WHO. These variants have several substitutions in the spike protein that affect receptor binding; they exhibit increased transmissibility and may be associated with reduced vaccine effectiveness. In the present work, we report the identification of a potential variant of interest, harboring the mutations T478K, P681H, and T732A in the spike protein, within the newly named lineage B.1.1.519, that rapidly outcompeted the preexisting variants in Mexico and has been the dominant virus in the country during the first trimester of 2021.

Challenges of diagnostic genomics in Latin America.

Cancer genome sequencing methods have now become essential for diagnostic purposes, for devising treatment strategies, and for monitoring disease regression and progression. However, access to these benefits has not permeated homogeneously throughout the world; certain regions, such as Latin America, have been slower at adopting these technologies in terms of their routine use, development and patient access. There are also differences among Latin American subregions with respect to their prioritized types of neoplasia and the drugs that are available and approved in them. An overview of the current situation, including the status of genomics for cancer diagnostics and efforts by type of cancer is presented. In addition, we discuss the perspective of initiatives, alliances, and educational/research programs that pledge to make cancer genomics diagnosis a reality for Latin American individuals' health.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Cryptorchidism and Testicular Tumor: Comprehensive Analysis of Common Clinical Features and Search of SNVs in the KIT and AR Genes.

Allelic variants in genes implicated in the development of testicular germ cell tumor (TGCT) could be present in patients with cryptorchidism (CO). Currently; the mechanisms explaining this relationship are still unknown. In this study the common clinical features in patients with CO and TGCT and 6 variants of KIT and AR genes associated to TGCT were analyzed. Population analyzed included 328 individuals: 91 patients with CO; 79 with TGCT, 13 of them with previous CO diagnosis, and 158 healthy males. Of the 13 patients with TGCT and history of CO, one patient (7.7%) presented the heterozygous form of the variant rs121913507 and two patients (15.4%) presented homozygote genotype for the variant rs121913506 in KIT gene. Interestingly, the heterozygous form for the variant rs121913506 of KIT gene was identifying in all of 13 patients. The rs201934623, rs774171864, and rs12014709 variants of the AR gene did not show any clinical association. Our results strongly support that genetic component in CO could be conditioning for the development of TGCT. Notably, KIT gene variants might be determinants in the pathological association between TGCT and CO.

Tumor microenvironment differences between primary tumor and brain metastases.

The present review aimed to discuss contemporary scientific literature involving differences between the tumor microenvironment (TME) in melanoma, lung cancer, and breast cancer in their primary site and TME in brain metastases (BM). TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, natural killer cells, and other cells can perpetuate and progress carcinogenesis via the secretion of molecules. Oxygen concentration, growth factors, and receptors in TME initiate angiogenesis and are examples of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant brain tumors are metastatic in origin and primarily originate from lung cancer, breast cancer, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood-brain barrier (BBB). After traversing BBB, these cells have to survive by producing various cytokines, chemokines, and mediators to modify their new TME. The microenvironment of these metastases is currently being studied owing to the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in BM due to several factors, including BBB. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might help improve strategies to comprehend cancer.

Mexican BRCA1 founder mutation: Shortening the gap in genetic assessment for hereditary breast and ovarian cancer patients.

The deletion of exons 9 to 12 of BRCA1 (9-12 del BRCA1) is considered a founder mutation in the Mexican population. We evaluate the usefulness of the target detection of 9-12 del BRCA1 as the first molecular diagnostic strategy in patients with Hereditary Breast and Ovarian Cancer (HBOC). We performed the genetic assessment of 637 patients with suspected HBOC. The region corresponding to the breakpoints for the 9-12 del BRCA1 was amplified by polymerase chain reaction (PCR). An analysis of the clinical data of the carriers and non-carriers was done, searching for characteristics that correlated with the deletion. The 9-12 del BRCA1 was detected in 5% of patients with suspected HBOC (30/637). In patients diagnosed with ovarian cancer, 13 of 30 were 9-12 del BRCA1 carriers, which represents 43%. We found a significant association between the 9-12 del BRCA1 carriers with triple negative breast cancer and high-grade papillary serous ovarian cancer. We concluded that the detection of the 9-12 del BRCA1 is useful as a first molecular diagnostic strategy in the Mexican population. In particular, it shortens the gap in genetic assessment in patients with triple negative breast cancer and ovarian cancer.

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.