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PubMed2026

Genomic landscape of autism spectrum disorder in Brazil.

Genomic studies of autism spectrum disorder (ASD) have largely excluded admixed populations. To address this gap, we characterized the genomic landscape of ASD in Brazil by combining a systematic literature review with whole-exome sequencing analysis of 441 Brazilian individuals and their families. Our analysis revealed a conclusive molecular diagnosis in 13.1% of probands. The diagnostic yield was higher among individuals with clinical features, particularly comorbid signs of intellectual disability, hypotonia, and seizures, providing a basis for prioritizing genetic testing. The sample presented a diverse ancestry, with major European, African, and Native American contributions. Notably, more than half of the identified rare risk variants were located on non-European haplotypes. Both de novo and inherited variants contributed to ASD risk, and we reinforce NPAS3 as a candidate ASD risk gene. This study provides the first comprehensive genomic overview of ASD in a large Brazilian cohort, reinforcing the critical need to include diversely admixed populations in genomic research to expand the understanding of ASD architecture and improve diagnostic strategies in resource-limited settings.

Journal Article↗

PubMed2026

Tumor genomic landscape of older patients with metastatic breast cancer☆.

BACKGROUND: Metastatic breast cancer (MBC) in older patients has distinct clinical and histologic characteristics. Elucidating the genomic basis of MBC helps identify potential therapeutic targets to improve outcomes for older patients with MBC. PATIENTS AND METHODS: Using a prospective database and targeted DNA sequencing (OncoPanel), we examined MBC's genomic landscape in older patients (age ≥70 years at MBC diagnosis) and compared findings with those in younger (aged <50 years) and middle-aged (aged 50-69 years) patients. After classifying single nucleotide variants (SNVs) and copy number variations (CNVs) as oncogenic (via OncoKB), the frequencies of SNVs and CNVs, tumor mutational burden (TMB), and oncogenic signaling pathways were compared by age group using Fisher's exact tests. We estimated the association between continuous age at MBC diagnosis and mutations via multivariate logistic regression analysis, adjusting for race, stage at initial diagnosis, subtype, histology, and sample tested (primary versus metastatic). RESULTS: Our study included 2379 patients [853 (35%) younger, 1311 (55%) middle-aged, and 215 (9%) older] who underwent OncoPanel testing between 2013 and 2020. The most frequent tumor alterations in older patients were SNVs in PIK3CA (44%), TP53 (33%), CDH1 (22%) and amplifications in CCND1 (18%). After adjustment, older age was associated with higher frequency of SNVs in CDH1 [odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.21-1.68, q < 0.001], MAP3K1 [OR = 1.30, 95% CI 1.10-1.54, q = 0.008], and PIK3CA [OR = 1.21, 95% CI 1.11-1.31, q < 0.001] and fewer SNVs in TP53 [OR = 0.84, 95% CI 0.77-0.91, q < 0.001]. Patients in the older group were more likely to have tumors with ≥10 mutations/megabase than the youngest patients (26% versus 17%, P = 0.003). CONCLUSIONS: In this large cohort of patients with MBC, the tumor genomic landscape differed between older and younger patients even after accounting for tumor subtype. Older patients were more likely to have high-TMB and PIK3CA-mutated tumors, highlighting the importance of genomic testing for treatment applications in this population.

NGS↗

PubMed2024

Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing. METHODS: Whole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}. RESULTS: Mutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes-identified across 10 genome sequencing studies-in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC. CONCLUSION: Our results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients.

Humans↗

PubMed2024

Genetic diversity, disease resistance, and environmental adaptation of Arachis duranensis L.: New insights from landscape genomics.

The genetic diversity that exists in natural populations of Arachis duranensis, the wild diploid donor of the A subgenome of cultivated tetraploid peanut, has the potential to improve crop adaptability, resilience to major pests and diseases, and drought tolerance. Despite its potential value for peanut improvement, limited research has been focused on the association between allelic variation, environmental factors, and response to early (ELS) and late leaf spot (LLS) diseases. The present study implemented a landscape genomics approach to gain a better understanding of the genetic variability of A. duranensis represented in the ex-situ peanut germplasm collection maintained at the U.S. Department of Agriculture, which spans the entire geographic range of the species in its center of origin in South America. A set of 2810 single nucleotide polymorphism (SNP) markers allowed a high-resolution genome-wide characterization of natural populations. The analysis of population structure showed a complex pattern of genetic diversity with five putative groups. The incorporation of bioclimatic variables for genotype-environment associations, using the latent factor mixed model (LFMM2) method, provided insights into the genomic signatures of environmental adaptation, and led to the identification of SNP loci whose allele frequencies were correlated with elevation, temperature, and precipitation-related variables (q < 0.05). The LFMM2 analysis for ELS and LLS detected candidate SNPs and genomic regions on chromosomes A02, A03, A04, A06, and A08. These findings highlight the importance of the application of landscape genomics in ex situ collections of peanut and other crop wild relatives to effectively identify favorable alleles and germplasm for incorporation into breeding programs. We report new sources of A. duranensis germplasm harboring adaptive allelic variation, which have the potential to be utilized in introgression breeding for a single or multiple environmental factors, as well as for resistance to leaf spot diseases.

Arachis↗

PubMed2026

Genomic Landscape of Metastatic Urothelial Cancer in a Multicenter Cohort From Argentina.

PURPOSE: The genomic landscape of advanced urothelial carcinoma (aUC) has enabled the development of targeted therapies; however, real-world data from Latin America remain limited. MATERIALS AND METHODS: We conducted a multicenter retrospective study including patients with aUC who underwent next-generation sequencing on tumor tissue. Molecular alterations were classified according to the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT). RESULTS: A total of 107 patients were included. Overall, 68 patients (63.6%) harbored at least one potentially actionable molecular alteration. Among these, 34 patients (31.8%) exhibited ESCAT level I alterations, most commonly involving FGFR3 mutations/fusions and ERBB2 amplification. CONCLUSION: A clinically meaningful proportion of Argentine patients with aUC harbor ESCAT level I actionable alterations, supporting the incorporation of routine genomic profiling into clinical practice.

Humans↗

PubMed2026

Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.

Carriers of germline BRCA1/2 pathogenic variants (gBRCA1/2 PVs) have elevated young-onset breast cancer risk. To define the pretreatment genomic landscapes of young-onset gBRCA-associated breast cancer, we evaluated 136 treatment-naive tumors diagnosed before age 50 in the prospective POSH study and 66 noncarriers from The Cancer Genome Atlas. Using whole-exome sequencing, we analyzed somatic variation, allele-specific loss of heterozygosity (asLOH), homologous recombination deficiency (HRD), and single-base substitution (SBS) signatures. gBRCA1 and gBRCA2 breast cancers had high rates of asLOH but differed significantly in average HRD scores and median SBS composition of signatures SBS1 (aging-associated), SBS18 (ROS-associated), and SBS3 (HRD-associated). Compared with gBRCA2 tumors, gBRCA1 tumors with asLOH were significantly enriched for alterations in hallmark ROS, DNA repair, and epithelial-mesenchymal transition pathways. In ER-positive, HER2-negative tumors from gBRCA1/2 carriers compared with noncarriers, we found significant enrichment of RB1, TP53, FAT1, and MYC single-nucleotide variants, indels, and copy number variants associated with CDK4/6 inhibitor (CDK4/6i) resistance. Together, these findings demonstrate significant differences between gBRCA1- and gBRCA2-associated breast cancers, and preexisting CDK4/6i resistance mechanisms, supporting prospective trials comparing individualized therapy for gBRCA1 versus gBRCA2 carriers and comparing poly(ADP-ribose) polymerase inhibitors versus CDK4/6i for ER-positive gBRCA1/2-associated breast cancer.

Humans↗

PubMed2006

The genomic landscape of histone modifications in human T cells.

To understand the molecular basis that supports the dynamic gene expression programs unique to T cells, we investigated the genomic landscape of activating histone modifications, including histone H3 K9/K14 diacetylation (H3K9acK14ac), H3 K4 trimethylation (H3K4me3), and the repressive histone modification H3 K27 trimethylation (H3K27me3) in primary human T cells. We show that H3K9acK14ac and H3K4me3 are associated with active genes required for T cell function and development, whereas H3K27me3 is associated with silent genes that are involved in development in other cell types. Unexpectedly, we find that 3,330 gene promoters are associated with all of these histone modifications. The gene expression levels are correlated with both the absolute and relative levels of the activating H3K4me3 and the repressive H3K27me3 modifications. Our data reveal that rapidly inducible genes are associated with the H3 acetylation and H3K4me3 modifications, suggesting they assume a chromatin structure poised for activation. In addition, we identified a subpopulation of chromatin regions that are associated with high levels of H3K4me3 and H3K27me3 but low levels of H3K9acK14ac. Therefore, these regions have a distinctive chromatin modification pattern and thus may represent a distinct class of chromatin domains.

Acetylation↗

PubMed2025

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3 km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change↗

PubMed2026

Understanding Genomic Landscapes of Differentiation in Round-Tailed Horned Lizards (Phrynosoma modestum).

Population divergence is promoted by divergent selection and inhibited by gene flow, but the mechanisms of and relationship between these two processes remain poorly understood. Developing a well-informed hypothesis of the selective pressures underlying divergence in a natural population requires a thorough understanding of both species structure and demographic history. In this study, we assess whole-genome sequences of round-tailed horned lizards (Phrynosoma modestum) from throughout the species range and combine phylogenetic analyses with genomic landscape scans to understand how current genetic diversity has been influenced by demographic histories and evolutionary pressures. Maximum likelihood (ML) phylogenetic analysis supports two lineages within the species, corresponding to a North/South population divide that developed around 7 million years ago (Ma) and displays little migration. However, intermediate genealogical divergence index values between the two lineages ultimately leave us unable to recommend a full taxonomic distinction. Genome-wide scans of population genetic statistics identified islands of divergence exhibiting differentiation patterns linked to models of reproductive isolation and within-population selection. Significantly negative values of Tajima's D and positive selection statistics in these islands offer support for selection acting on P. modestum, but patterns may also stem from recent population expansions. We posit that selection within populations has played a large role in shaping genomic divergence across the species' range. Taken together, our results provide perspective into how variable selective pressures shape the genomics of two divergent populations currently maintaining species integrity, despite significant signatures of geographic structure and divergence.

Animals↗

PubMed2024

Comparative genomic landscape of lower-grade glioma and glioblastoma.

Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1-wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10, for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

Humans↗

PubMed2026

Landscape Genomics Reveals Divergent Adaptation Modes and Predicts Climate Vulnerability in Xinjiang Indigenous Sheep.

Climate change increasingly endangers precious indigenous sheep germplasm resources distributed across diverse Chinese landscapes, and systematically decoding their polygenic climate-adaptive genetic mechanisms is essential for targeted breed conservation and long-term sustainable pastoral production. Whole-genome resequencing data from 93 individuals covering six representative local sheep breeds were analyzed in this work. After filtering highly collinear climate variables, three mature landscape genomic approaches were jointly applied to identify environment-linked gene variants, while two predictive metrics across ten CMIP6 future climate scenarios quantified each breed's long-term adaptive risks. Six temperature- and water-related environmental factors jointly drove sheep population genetic differentiation, with temperature fluctuation indices showing markedly stronger explanatory power. Detected adaptive genes were significantly enriched in ion transport, energy metabolism and cellular stress response pathways. Future projections indicated western breeds (Bayinbuluke, Cele Black, Xiahe) face severe maladaptation risks under high-emission SSP370 scenarios by 2100, whereas central and eastern breeds possess much broader climate tolerance. This study systematically reveals the core genomic basis of ovine climate adaptation and quantifies distinct breed-specific climate vulnerability, providing solid reliable theoretical support for precision germplasm conservation and selective breeding of climate-resilient sheep varieties.

adaptive loci↗

PubMed2025

Unveiling the Genomic Landscape of Escherichia coli O1:K1:H7 ST59 in Non-complicated Urinary Infections from Colombia Through Whole-Genome Sequencing.

Escherichia coli (E. coli) is a Gram-negative bacterium known for causing both intestinal and extraintestinal infections in humans. Among extraintestinal infections, urinary tract infections (UTIs) are particularly prevalent and impactful. In Colombia, limited information is available regarding the molecular epidemiology of E. coli. This lack of data hinders the understanding of the local epidemiological landscape and the identification of pathogenic lineages that may contribute to public health concerns. This study aimed to characterize an E. coli strain isolated from a 24-year-old female patient with a community-acquired lower UTI, focusing on genotypic analysis through whole-genome shotgun sequencing (WGSS) and subsequent bioinformatics investigations. The identified strain belongs to phylogroup F, with serotype O1:H7 and sequence type (ST) 59. Several virulence factors, including traT and afimbrial adhesins (afaC), were identified, with afaC being notably uncommon in ST59 phylogroup F. In addition, an antibiotic susceptibility test was performed, and the isolate was found to be sensitive to all the antibiotics tested. This work contributes to the understanding of E. coli phylogroup F in Colombia and provides valuable genomic data, shedding light on the virulence profile of this strain in lower urinary tract infections.

Female↗

PubMed2001

Http://C. elegans: mining the functional genomic landscape.

Caenorhabditis elegans is a powerful animal model for the study of functional genomics. The completed and well-annotated DNA sequence is available and a systematic study of gene function by RNA-interference-mediated knockdown of every gene is in progress. Full-genome DNA microarrays and DNA chips can be used to determine expression changes at different stages of development and in different mutant backgrounds, and a protein-interaction map based on the yeast two-hybrid approach is in progress. These high-capacity approaches to studying gene function will provide new insights into invertebrate and vertebrate biology.

Animals↗

PubMed2026

Population and landscape genomics provide insights into the adaptive genetic variation and future climate-induced vulnerability of the endangered tree species Phoebe bournei.

Elucidating the genomic underpinnings of adaptive variation is highly important for the conservation, landscape application, and management of ornamental trees against the backdrop of global climate change. However, research on the genetic mechanisms underlying climate adaptation in Phoebe bournei-a near-threatened subtropical tree species endemic to China, which is endowed with exceptionally high ornamental and ecological value-remains scarce. Whole-genome resequencing was conducted on 362 individuals from 27 natural populations across the geographical range of the species. Genome-environment association analyses were employed to identify 1556 climate-associated variants and 167 candidate genes associated with temperature and precipitation variables. Through functional annotation and expression profiling, pivotal genes, including TRX-M4 and FBD1, were identified as integral to drought and heat stress responses, with adaptive alleles displaying distinct geographic frequency distributions and significant phenotypic differentiation. Divergent evolutionary trajectories were deduced among populations, with southeastern populations distinguished by elevated genetic diversity and strong signatures of local adaptation. Nevertheless, projections derived from the Risk of Non-Adaptedness and gradient forest models suggest that these southeastern populations will face substantial genomic offset under future climate scenarios, signaling heightened vulnerability and the need for prioritized conservation and management. This study provides the first genome-wide perspective into the adaptive evolution of P. bournei and offers a robust foundation for its conservation and climate-resilient management.

Journal Article↗

PubMed2025

Investigating the genomic landscape of mouse models of breast cancer metastasis.

Metastasis remains a major cause of cancer mortality. AbstractThis study, expanding upon previous findings in the MMTV-PyMT model, investigated four independent mouse models, representing luminal (MMTV-PyMT, MMTV-Myc), HER2-amplified (MMTV-Her2) and triple negative (C3(1)TAg) breast cancer subtypes. Consistent with previous results, limited evidence for metastasis-associated somatic point mutations was found for all models. We also found that oncogenic drivers significantly influenced the number and size of metastasis-specific copy number variations (MSCNVs), but common driver-independent MSCNVs were rare. Furthermore, analyzing a cohort with varying genetic backgrounds while maintaining a constant oncogenic driver (PyMT) revealed that genetic background profoundly impacts MSCNVs. Transcriptome analysis demonstrated that oncogenic drivers strongly shaped metastasis-specific gene expression (MSGE), with each driver exhibiting distinct expression profiles. In contrast, MSGE in the PyMT-F1 cohort was more variable across strains. Despite the diversity of MSCNV and MSGE, functional analysis revealed that both mechanisms converge on the modulation of key cellular processes, including immune responses, metabolism, and extracellular matrix interactions. These findings emphasize the complex interplay between oncogenic drivers and genetic background in shaping the genomic and transcriptional landscapes of metastatic lesions.

Journal Article↗

PubMed2026

Deciphering the genomic landscape of novel Acinetobacter non-baumannii lineages causing neonatal septicemia: carbapenem resistance and virulence.

BACKGROUND: Acinetobacter non-baumannii (Anb) species are reported worldwide to cause infections in both adults and neonates, although less frequently than Acinetobacter baumannii. However, limited information is available on their genomic diversity, resistance mechanisms, and virulence potential. This study investigates novel Anb isolates causing neonatal septicemia in India to characterize their resistance and pathogenic traits. METHODS: Anb isolates from neonatal blood cultures (2007-2025) were identified by VITEK2 Compact system, MALDI-TOF MS, and Whole-genome sequencing (WGS). Antimicrobial susceptibility was tested by VITEK2. Genomic analysis included MLST, resistome, virulome, plasmid typing, integrons, and core-genome phylogeny analysis. In vitro and in vivo studies assessed pathogenic potential of Anb species. RESULTS: Anb infections were low (11%) among the neonates during the study period. WGS revealed 11 novel Sequence Types (STs) which include A. indicus, A. variabilis, A. schindleri, and A. bereziniae. Six out of these eleven Anbs harbored carbapenemases such as bla NDM-1 and/or bla OXA-58-like genes (bla OXA-58, bla OXA-420). bla NDM-1 was acquired via Tn125 transposon. ISAba125 was located upstream of bla NDM-1, and a conserved structure extending to IS91 family transposase was detected in bla NDM-1-harboring genomes. bla OXA-58-like genes were found to be associated with ISAba3. Most carbapenemases were likely located on chromosome. Class 1 integrons carrying multiple antimicrobial resistance genes (ARGs) and diverse plasmid replicase families were detected in Anbs. Core genome phylogeny showed that the study Anbs were not closely related to the global Anbs. In vitro virulence-associated assays (biofilm formation, surface motility, adherence/invasion, apoptosis) and in vivo lethality in murine infection model showed reduced pathogenicity, reinforcing earlier observations that Anb species are generally less virulent than A. baumannii. Several virulence factors (VFs) were detected; however, no clear correlation was observed between virulence genes, in vitro pathogenicity, and in vivo lethality. CONCLUSION: These results indicate the multifactorial nature of Anb pathogenicity and the current limitations of knowledge of its VFs. However, the presence of numerous VFs suggests a capacity to cause disease, particularly in vulnerable host populations such as neonates. Furthermore, the presence of multiple ARGs indicates a strong potential for persistence and dissemination in hospital environments with high antibiotic pressure. Overall, these findings underscore the importance of continued AMR surveillance, genome characterization and further investigations into Anb pathogenicity.

Acinetobacter non-baumannii↗

PubMed2026

The genomic landscape of HER2 negative metastatic breast cancer with loss of estrogen and progesterone receptors.

INTRODUCTION: Loss of estrogen receptor (ER) and/or progesterone receptor (PR) might occur during the metastatic progression of ER positive and HER2 negative (ER+/HER2-) breast cancer (BC), but the underpinning molecular alterations remain elusive. We explored the genomic context of HER2- tumors with ER and/or PR loss to investigate potential drivers and actionable alterations that might help personalize treatment of ER+/HER2- BC. METHODS: We accessed data from metastatic HER2- BC included in the MSK-2018 dataset to compare outcome, tumor characteristics and genomic alterations of BC with loss of ER (ER+/-, n = 66) to those maintaining ER positivity (ER+/+, n = 364) or ER negativity (ER-/-, n = 50). We also compared metastatic ER+/+ BC with loss of PR (PR+/-, n = 111) to those maintaining PR positivity (PR+/+, n = 192) or PR negativity (PR-/-, n = 41). RESULTS: In line with previous reports, ER+/- BC was associated with aggressive clinico-pathological characteristics and poor outcome. ER+/- BC showed significantly higher frequency of TP53 and RB1 mutations and lower frequency of PIK3CA and GATA3 mutations compared to ER+/+. ER+/- or PR+/- status was mutually exclusive with ESR1 mutations and was associated with a significantly higher tumor mutational burden. Moreover, ER+/- BC were enriched in driver alterations in the genes of the Notch and Retinoblastoma pathways and showed a significantly lower frequency of level 1 actionable alterations according to OncoKB. CONCLUSIONS: Loss of ER and/or PR may identify a distinct evolutionary trajectory of ER+/HER2- metastatic progression, largely non-overlapping with ESR1-mutant endocrine resistance. Further studies on matched primary and metastatic samples are warranted.

Humans↗

PubMed2026

Uncovering the genomic landscape of Mycobacterium bovis in Wales.

Bovine tuberculosis (bTB), caused by the bacterium Mycobacterium bovis, is one of the most pressing animal health issues in Wales today. It negatively impacts cattle health, affects profitability and trade, and can decimate years of genetic improvement towards desirable production traits. It also imposes substantial financial, social, and psychological burdens on farming communities. Eradication of bTB requires an understanding of local transmission pathways to target effective disease-control interventions. In this study, we characterised the genomic diversity of M. bovis across Wales by analysing the genome sequence of 379 M. bovis isolates obtained from culture-positive animals in Wales in 2021. Analyses uncovered three prevalent clusters that are geographically distinct. A further three clusters containing fewer isolates were also geographically separated, two of which had particularly large SNP distances from most other Welsh isolates, suggesting independent introductions of M. bovis strains that are not endemic to Wales. Fine-scale and epidemiologically relevant genetic structuring was identified within the six main clusters, indicating region-specific evolution, which can drive local disease dynamics. Finally, SNPs were identified in coding genes that have the potential for important advantageous physiological consequences that may impact host-pathogen interactions and necessitate further investigation.

Animals↗