The microbiome has shown a correlation with the diet and lifestyle of each population in health and disease, the ability to communicate at the cellular level with the host through innate and adaptative immune receptors, and therefore an important role in modulating inflammatory process related to the establishment and progression of cancer. The oral cavity is one of the most important interaction windows between the human body and the environment, allowing the entry of an important number of microorganisms and their passage across the gastrointestinal tract and lungs. In this review, the contribution of the microbiome network to the establishment of systemic diseases like cancer is analyzed through their synergistic interactions and bidirectional crosstalk in the oral-gut-lung axis as well as its communication with the host cells. Moreover, the impact of the characteristic microbiota of each population in the formation of the multiomics molecular metafirm of the oral-gut-lung axis is also analyzed through state-of-the-art sequencing techniques, which allow a global study of the molecular processes involved of the flow of the microbiota environmental signals through cancer-related cells and its relationship with the establishment of the transcription factor network responsible for the control of regulatory processes involved with tumorigenesis.

A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA–Phe233del showed that the occurrence of the Phe233del affects between 220–320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein–DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA–Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics–Molecular Mechanics (QM–MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Inflammation can positively and negatively affect tumorigenesis based on the duration, scope, and sequence of related events through the regulation of signaling pathways. A transcriptomic analysis of five pulmonary arterial hypertension, twelve Crohn’s disease, and twelve ulcerative colitis high throughput sequencing datasets using R language specialized libraries and gene enrichment analyses identified a regulatory network in each inflammatory disease. IRF9 and LINC01089 in pulmonary arterial hypertension are related to the regulation of signaling pathways like MAPK, NOTCH, human papillomavirus, and hepatitis c infection. ZNF91 and TP53TG1 in Crohn’s disease are related to the regulation of PPAR, MAPK, and metabolic signaling pathways. ZNF91, VDR, DLEU1, SATB2-AS1, and TP53TG1 in ulcerative colitis are related to the regulation of PPAR, AMPK, and metabolic signaling pathways. The activation of the transcriptomic network and signaling pathways might be related to the interaction of the characteristic microbiota of the inflammatory disease, with the lung and gut cell receptors present in membrane rafts and complexes. The transcriptomic analysis highlights the impact of several coding and non-coding RNAs, suggesting their relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during lung and gut cell adaptation to inflammatory phenotypes.

Background and Objectives: Neurodevelopmental disorders (NDDs), including developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), and specific learning disorders, affect 15% of children and adolescents worldwide. Advances in next-generation sequencing, particularly whole exome sequencing (WES), have improved the understanding of NDD genetics. Methodology: This study analyzed 3244 patients undergoing WES (single, duo, trio analyses), with 1028 meeting inclusion criteria (67% male; aged 0–50 years). Results: Pathogenic (P) or likely pathogenic (LP) variants were identified in 190 patients, achieving a diagnostic yield of 13.4% (singleton), 14% (duo), and 21.2% (trio). A total of 207 P/LP variants were identified in NDD-associated genes: 38% were missense (48 de novo), 29% frameshift (26 de novo), 21% nonsense (14 de novo), 11% splicing site (14 de novo), and 1% inframe (1 de novo). De novo variants accounted for 49.8% of cases, with 86 novels de novo variants and 27 novel non de novo variants unreported in databases like ClinVar or scientific literature. Conclusions: This is the largest study on WES in Colombian children with NDDs and one of the largest in Latino populations. It highlights WES as a cost-effective first-tier diagnostic tool in low-income settings, reducing diagnostic timelines and improving clinical care. These findings underscore the feasibility of implementing WES in underserved populations and contribute significantly to understanding NDD genetics, identifying novel variants with potential for further research and clinical applications.

Considerable fraction of global cancer cases stem from hereditary cancer predisposition syndromes (HCSs). The identification of genetic variants linked to HCSs is crucial for prompt treatment of both patients and their families. This study aimed to assess the diagnostic performance of multigene panels in detecting variants linked to hereditary cancer predisposition in a cohort of 8165 individuals from Colombia. We analyzed 8165 individuals in Colombia (2018–2024), with and without personal or family cancer history, using NGS hereditary cancer panels. Variant interpretation (P, LP, VUS) was performed with SOPHiA DDM and Varsome Clinical, following ACMG guidelines and ClinGen Hereditary Cancer Group criteria. 61.8% (n = 5049) of patients were referred from Bogotá and 38.10% (n = 3116) from other cities in Colombia. It was not possible to distinguish between ethnic groups. The age range of patients was 0–97 (mean = 55 years; SD = 12.1), 86% (n = 7024) were female and 14% (n = 1142) male. 409 P/LP variants were identified in high-penetrance genes such as BRCA1/2, in 946 individuals, resulting in an overall diagnostic yield of 9.82%. Among the most important findings were increased diagnostic yields in ovarian and colorectal cancer, as well as in unaffected individuals with a family history of cancer. Finally, 38 novel variants and recurrent alterations in 27 HCS-related genes reinforce the need to prioritize these biomarkers in diagnostic evaluations. This study provides insights into the performance of genetic panels for detecting HCS-associated variants in the largest Latin American cohort evaluated to date. These findings demonstrate that robust panel-based testing strategies enable the systematic detection of clinically relevant signs that would not be captured through phenotype-driven approaches alone. BRCA1 and BRCA2 were the most frequently altered high-penetrance genes, with higher diagnostic yields in breast, ovarian, and colorectal cancers, as well as in unaffected individuals with a family history. Fundación Universitaria Sanitas.

Background/Objectives: The oral–gut–lung axis represents a dynamic system where exosomes carrying mRNAs and non-coding RNAs might help to regulate microbiota and human cell crosstalk to establish transcriptional regulatory networks controlling cellular biological processes and signaling pathways. Methods: We conducted a comprehensive transcriptomic analysis to characterize the molecular cargo of extracellular exosomes in the context of gut and lung cancer. Results: By analyzing gut and lung exosomes cargo with our previous transcriptomic studies from tumoral and inflammatory tissues, we found that exosomes can transport key RNAs that codify specific receptors that facilitate pathogenic interaction with microorganisms and RNAs that are part of interacting gene and transcriptional regulatory networks that control the function of differentially expresses genes, all involved in biological processes like cell cycle, plasticity and growth regulation, invasion, metastasis, microenvironmental remodeling, epigenetic, and microbial and immunological modulation, during the unlocking of phenotypic plasticity for the acquisition of the hallmarks of cancer in the oral–gut–lung axis. Conclusions: Exosomal RNA regulation of transcriptional networks represents a pivotal axis in the interplay between inflammation and cancer, offering opportunities for innovative diagnostic and therapeutic approaches.