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(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer's development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes.

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Here, we report the draft genome sequences of 4 Bordetella pertussis isolates which correspond to major clones isolated between 2008 and 2014 from two outbreaks in northeastern Mexico. The B. pertussis clinical isolates belong to the ptxP3 lineage, and they are grouped into two major clusters, defined by the fimH allele.

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Purpose: To evaluate whether changes in genomic expression that occur beginning with breast cancer (BC) diagnosis and through to tumor resection after neoadjuvant chemotherapy (NCT) reveal biomarkers that can help predict therapeutic response and survival. Materials and Methods: We determined gene expression profiles based on microarrays in tumor samples from 39 BC patients who showed pathologic complete response (pCR) or therapeutic failure (non-pCR) after NCT (cyclophosphamide-doxorubicin/epirubicin). Based on unsupervised clustering of gene expression, together with functional enrichment analyses of differentially expressed genes, we selected NUSAP1, PCLAF, MME, and DST. We evaluated the NCT response and the expression of these four genes in BC histologic subtypes. In addition, we study the presence of tumor-infiltrating lymphocytes. Finally, we analyze the correlation between NUSAP1 and PCLAF against disease-free survival (DFS) and overall survival (OS). Results: A signature of 43 differentially expressed genes discriminated pCR from non-pCR patients (|fold change >2|, false discovery rate <0.05) only in biopsies taken after surgery. Patients achieving pCR showed downregulation of NUSAP1 and PCLAF in tumor tissues and increased DFS and OS, while overexpression of these genes correlated with poor therapeutic response and OS. These genes are involved in the regulation of mitotic division. Conclusions: The downregulation of NUSAP1 and PCLAF after NCT is associated with the tumor response to chemotherapy and patient survival.

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Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.

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Resumen Introducción: Variantes génicas relacionadas con la vía de señalización de las proteínas morfogenéticas óseas (BMP2, BMP4, GREM1, SMAD7) se han asociado a cáncer colorrectal, principalmente en poblaciones caucásicas. Objetivo: Describir la asociación de variantes en miembros de la vía BMP en población mexicana, caracterizada por su ancestría indoamericana y caucásica. Métodos: Se realizó el genotipado de 1000 casos de cáncer colorrectal y 1043 individuos de control reclutados en la Ciudad de México, Monterrey y Torreón mediante la plataforma Sequenom. Con análisis univariados y multivariados se estudiaron las asociaciones entre cáncer colorrectal y variantes. Resultados: Las variantes rs4444235, rs12953717 y rs4939827 replicaron la asociación con la neoplasia (p ≤ 0.05). La ascendencia caucásica mostró asociación con el tumor. Conclusiones: El estudio mostró las asociaciones entre cáncer colorrectal y las variantes SMAD7 y BMP4, así como con el componente caucásico de la mezcla étnica.

Abstract Introduction: Genetic variants related to bone morphogenetic proteins (BMP2, BMP4, GREM1, SMAD7) signaling pathway have been associated with colorectal cancer, mainly in Caucasian populations. Objective: To describe the association of variants in members of the BMP signaling pathway in a Mexican population, characterized by its indigenous American and Caucasian ancestry. Methods: Genotyping of 1,000 colorectal cancer cases and 1,043 control individuals recruited in Mexico City, Monterrey, and Torreón was carried out using the Sequenom platform. Associations between colorectal cancer and variants were studied with univariate and multivariate analyses. Results: Variants rs4444235, rs12953717 and rs4939827 replicated the association with the neoplasm (p ≤ 0.05). Caucasian ancestry showed association with the tumor. Conclusions: The study replicated the associations between colorectal cancer and SMAD7 and BMP4 variants, with an association being observed with the Caucasian component of the ethnic mix.

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No genetic basis is currently established that differentiates hypermobility spectrum disorders (HSD) from hypermobile Ehlers-Danlos syndrome (hEDS). Diagnosis is entirely based on clinical parameters with high overlap, leading to frequent misdiagnosis of these two phenotypes. This study presents a landscape of DNA mutations through whole-exome sequencing of patients clinically diagnosed with generalized HSD. In this study, three genes (MUC3A, RHBG, and ZNF717) were mutated in all five patients evaluated. The functional enrichment analysis on all 1162 mutated genes identified the extracellular matrix (ECM) structural constituent as the primary overrepresented molecular function. Ingenuity pathway analysis identified relevant bio-functions, such as the organization of ECM and hereditary connective tissue disorders. A comparison with the matrisome revealed 55 genes and highlighted MUC16 and FREM2. We also contrasted the list of mutated genes with those from a transcriptomic analysis on data from Gene Expression Omnibus, with only 0.5% of the genes at the intersection of both approaches supporting the hypothesis of two different diseases that inevitably share a common genetic background but are not the same. Potential biomarkers for HSD include the five genes presented. We conclude the study by describing five potential biomarkers and by highlighting the importance of genetic/genomic approaches that, combined with clinical data, may result in an accurate diagnosis and better treatment.

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Maternal nutritional programming by energy-dense foods leads to the transgenerational heritance of addiction-like behavior. Exposure to energy-dense foods also activates systemic and central inflammation in the offspring. This study aimed to characterize pro- and anti-inflammatory cytokine profiles in blood and their correlation to the transgenerational heritance of the addiction-like behavior in rats. F1 offspring of male Wistar diagnosed with addiction-like behavior were mated with virgin females to generate the F2 and the F3 offspring, respectively. Diagnosis of addiction-like behavior was performed by the operant training schedule (FR1, FR5 and PR) and pro- and anti-inflammatory cytokine profiles in blood were measured by multiplex platform. Multiple linear models between behavior, fetal programming by diet and pro- and anti-inflammatory cytokine profiles were performed. We found that the addiction-like behavior found in the F1 male offspring exposed to energy-dense food (cafeteria, CAF) diet during fetal programing is transgenerational inherited to the F2 and F3 generations. Blood from addiction-like behavior subjects of F2 and F3 generations exposed to CAF diet during maternal programming showed decrease in the anti-inflammatory IL-10 in the plasma. Conversely, decreased levels of the pro-inflammatory MCP-1 was identified in non-addiction-like subjects. No changes were found in plasmatic TNF-α levels in the F2 and F3 offspring of non-addiction-like and addiction-like subjects. Finally, biological modeling between IL-10 or MCP-1 plasma levels and prenatal diet exposure on operant training responses confirmed an association of decreased IL-10 levels on addiction-like behavior in the F2 and F3 generations. Globally, we identified decreased anti-inflammatory IL-10 cytokine in the blood of F2 and F3 offspring subjects diagnosed with addiction-like behavior for food rewards.

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Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.

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Breast cancer (BC) is one of the most frequent cancer types in women worldwide. About 7% is diagnosed in young women (YBC) less than 40 years old. In Mexico, however, YBC reaches 15% suggesting a higher genetic susceptibility. There have been some reports of germline variants in YBC across the world. However, there is only one report from a Mexican population, which is not restricted by age and limited to a panel of 143 genes resulting in 15% of patients carrying putatively pathogenic variants. Nevertheless, expanding the analysis to whole exome involves using more complex tools to determine which genes and variants could be pathogenic. We used germline whole exome sequencing combined with the PeCanPie tool to analyze exome variants in 115 YBC patients. Our results showed that we were able to identify 49 high likely pathogenic variants involving 40 genes on 34% of patients. We noted many genes already reported in BC and YBC worldwide, such as BRCA1, BRCA2, ATM, CHEK2, PALB2, and POLQ, but also others not commonly reported in YBC in Latin America, such as CLTCL1, DDX3X, ERCC6, FANCE, and NFKBIE. We show further supporting and controversial evidence for some of these genes. We conclude that exome sequencing combined with robust annotation tools and further analysis, can identify more genes and more patients affected by germline mutations in cancer.

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INTRODUCTION: Group B Streptococcus (GBS) causes infections in women during pregnancy and puerperium and invasive infections in newborns. The genes lmb, cylE, scpB, and hvgA are involved with increased virulence of GBS, and hypervirulent clones have been identified in different regions. In addition, increasing resistance of GBS to macrolides and lincosamides has been reported, so knowing the patterns of antibiotic resistance may be necessary to prevent and treat GBS infections. This study aimed to identify virulence genes and antibiotic resistance associated with GBS colonization in pregnant women from northeastern Mexico. METHODS: Pregnant women with 35-37 weeks of gestation underwent recto-vaginal swabbing. One swab was inoculated into Todd-Hewitt broth supplemented with gentamicin and nalidixic acid, a second swab was inoculated into LIM enrichment broth, and a third swab was submerged into a transport medium. All samples were subcultured onto blood agar. After overnight incubation, suggestive colonies with or without hemolysis were analyzed to confirm GBS identification by Gram staining, catalase test, hippurate hydrolysis, CAMP test, and incubation in a chromogenic medium. We used latex agglutination to confirm and serotype GBS isolates. Antibiotic resistance patterns were assessed by Vitek 2 and disk diffusion. Periumbilical, rectal and nasopharyngeal swabs were collected from some newborns of colonized mothers. All colonized women and their newborns were followed up for three months to assess the development of disease attributable to GBS. Draft genomes of all GBS isolates were obtained by whole-genome sequencing. In addition, bioinformatic analysis to identify genes encoding capsular polysaccharides and virulence factors was performed using BRIG, while antibiotic resistance genes were identified using the CARD database. RESULTS: We found 17 GBS colonized women out of 1154 pregnant women (1.47%). None of the six newborns sampled were colonized, and no complications due to GBS were detected in pregnant women or newborns. Three isolates were serotype I, 5 serotype II, 3 serotype III, 4 serotype IV, and 2 serotype V. Ten distinct virulence gene profiles were identified, being scpB, lmb, fbsA, acp, PI-1, PI-2a, cylE the most common (3/14, 21%). The virulence genes identified were scpB, lmb, cylE, PI-1, fbsA, PI-2a, acp, fbsB, PI-2b, and hvgA. We identified resistance to tetracycline in 65% (11/17) of the isolates, intermediate susceptibility to clindamycin in 41% (7/17), and reduced susceptibility to ampicillin in 23.5% (4/17). The tetM gene associated to tetracyclines resistance was found in 79% (11/14) and the mel and mefA genes associated to macrolides resistance in 7% (1/14). CONCLUSIONS: The low prevalence of colonization and the non-occurrence of mother-to-child transmission suggest that the intentional search for GBS colonization in this population is not justified. Our results also suggest that risk factors should guide the use of intrapartum antibiotic prophylaxis. The detection of strains with genes coding virulence factors means that clones with pathogenic potential circulates in this region. On the other hand, the identification of decreased susceptibility to antibiotics from different antimicrobial categories shows the importance of adequately knowing the resistance patterns to prevent and to treat GBS perinatal infection.

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