SEARCH · PubMed Health

Results for “mutational profiling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2025

SISTEM: simulation of tumor evolution, metastasis, and DNA-seq data under genotype-driven selection.

SUMMARY: SISTEM is a software package and mathematical framework for simulating tumor evolution and cell migrations at single-cell resolution. Unlike existing frameworks which simulate cancer cell populations under the neutral coalescent or using simple birth-death models, SISTEM simulates tumor populations under somatic clonal selection using an agent-based framework. SISTEM can generate mutation profiles, read counts, and DNA sequencing reads along with ground truth cell lineages and migration graphs under a number of easily customizable mutation and selection models. For improved realism, SISTEM allows for cell fitness to be driven by genomic events of various scales including single nucleotide variants, segmental gains and losses, whole-chromosomal and chromosome-arm aberrations, and whole-genome duplications. SISTEM also includes numerous migration models to simulate metastatic cancers, facilitating the exploration and evaluation of diverse migration patterns. AVAILABILITY AND IMPLEMENTATION: SISTEM is written in Python and is freely available open-source under GNU GPLv3 from: https://github.com/samsonweiner/sistem.

Software↗

PubMed2026

Establishment of Stable Immortalized Human Choroidal Melanocytes for Ocular Research.

PURPOSE: The short lifespan of primary normal choroidal melanocytes (NCMs) in vitro represents a major barrier to mechanistic, functional, and translational studies of choroid biology and uveal melanoma (UM). This study aimed to establish and characterize immortalized human NCM lines that retain melanocytic function, maintain a non-cancerous profile, and are amenable to gene editing. METHODS: NCMs from four donors were immortalized by lentiviral transduction of cyclin-dependent kinase 4 (CDK4R24C), cyclin D1, and human telomerase reverse transcriptase (hTERT), establishing NCM-K4DT lines. Their morphology, melanocytic marker expression, proliferation, and functional properties (melanin synthesis and tyrosinase activity) were evaluated. Genomic stability was assessed by targeted mutation profiling, karyotyping, and copy number variation (CNV) analysis. The tumorigenicity was tested in immunodeficient mice. Plasmid-based CRISPR/Cas9 editing was performed to determine their suitability for gene editing. RESULTS: NCM-K4DT lines retained dendritic-shaped morphology, pigmentation, and expression of PMEL, TYRP1, Melan-A, and SOX10. Cells exhibited enhanced proliferative capacity with preserved cell cycle regulation. Melanin production and tyrosinase activity were comparable to primary NCMs. Genomic profiling confirmed the absence of UM-associated driver mutations and chromosomal abnormalities. In vivo growth assays demonstrated that NCM-K4DT lines did not form tumors within the 3-month observation period. Notably, NCM-K4DT cells were efficiently edited by CRISPR/Cas9. CONCLUSIONS: NCM-K4DT lines represent stable, non-cancerous, and genetically tractable models for studying choroidal melanocyte biology, modeling UM-associated mechanisms, and advancing therapeutic development in ocular research.

Humans↗

PubMed2025

Genomic and Transcriptomic Landscape of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma: A Multicenter Study.

Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV+ IFDCS) is a rare indolent malignant neoplasm, which occurs almost exclusively in the liver or spleen and may arise from a common EBV-infected mesenchymal cell that differentiates along the follicular or fibroblastic dendritic cell pathway. Despite its rarity, it presents a pressing need for an improved understanding of its genetic underpinnings and potential treatment strategies for recurrent or disseminated cases. To address this, we conducted comprehensive whole-exome sequencing and transcriptome sequencing (mRNA-seq) analyses on 31 and 6 cases of EBV+ IFDCS, respectively, collected from multiple centers in China. We also compared the genetic features of EBV+ IFDCS with those of other EBV-associated malignancies. Our analyses revealed a relatively high somatic mutation rate and widespread copy number variations affecting the major histocompatibility complex-I/II in EBV+ IFDCS. Integrated mutational profiling identified key signaling pathways involved in epigenetic regulation, NF-κB signaling, RTK/RAS/PI(3)K, and the Hippo pathway. Furthermore, we identified several frequently altered genes that could serve as potential therapeutic targets in EBV+ IFDCS. Transcriptomic analysis unveiled significant upregulation of pathways related to virus infection, immune responses, and multiple immune checkpoint genes in EBV+ IFDCS. Comparative analysis demonstrated clear genetic distinctions between EBV+ IFDCS and other EBV-associated tumors. In conclusion, our study provides comprehensive insights into the unique genomic and transcriptomic landscape of EBV+ IFDCS. We have identified multiple genetic alterations that likely contribute to the development and progression of this malignancy. Our results suggest that targeted therapy and immune checkpoint inhibitors may hold promise as potential therapeutic approaches for patients with recurrent or disseminated EBV+ IFDCS.

Humans↗

PubMed2026

Complete Genome Sequencing of Occult Hepatitis B Virus in Hemodialysis Patients Reveals Subgenotype D2 and Immune Escape Mutations in Bangladesh.

Hepatitis B virus (HBV) remains a major global health concern, and occult HBV infection (OBI) presents significant diagnostic and clinical challenges, particularly among hemodialysis (HD) patients. This study is aimed at characterizing complete HBV genomes from maintenance HD patients with OBI in Bangladesh to elucidate genetic features, mutational patterns, and clinical implications. Serum samples from two HBsAg-negative HD patients were screened by ELISA and quantitative PCR. Viral DNA was amplified by PCR across four overlapping open reading frames (ORFs) and sequenced on the Illumina platform. Genome assembly, phylogenetic analysis, and mutational profiling were performed using reference datasets and bioinformatics tools. Antigenicity and hydrophilicity of HBsAg were predicted in silico. Both patients were anti-HBc and anti-HBs positive with high HBV DNA loads (2.29 × 1010 and 2.53 × 1010 copies/mL). Full-length genomes (3182 bp) were successfully sequenced and phylogenetic analysis showed both HBV genomes clustered within Genotype D, Subgenotype D2, and subtype ayw3, consistent with previously reported Bangladeshi HBV genomes. Comparative mutational analysis identified substitutions such as T1753C in the basal core promoter, C1845T in preC, and D144E within the "a" determinant of HBsAg, suggesting potential roles in vaccine escape, immune escape, and diagnostic failure. Several nonsynonymous mutations were also detected in polymerase, though none were potentially associated with antiviral resistance. Antigenicity and hydrophilicity profiles of HBsAg and its major hydrophilic region remained largely conserved. These findings demonstrate the persistence of OBI in HD patients and provide an initial indication of the need for genomic surveillance to monitor immune-escape mutations and improve HBV diagnostic strategies in endemic regions.

HBV genome sequencing↗

PubMed2026

Motif-centered analyses reveal universal and tissue-specific mutagenic mechanisms operating in the human body.

Somatic mutations are inevitable in human genomes and can lead to cancer initiation and tumor progression. Although many mutagenic processes have been linked to cancer, their activities in normal tissues before malignant transformation remain poorly characterized. Here, we analyzed the mutation profiles of 10,625 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C→T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We also identified a second clock-like motif, T→C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Motifs associated with other environmental and chemical mutagens showed sporadic and tissue-specific mutagenesis. APOBEC-induced C→T and C→G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most tissues. Together, our analyses elucidated several cancer-associated mutagenic processes in normal tissues and provided a robust analytical framework for quantifying mutagenic activities from somatic mutation catalogs.

Humans↗

PubMed2026

Motif-Centered Analyses Reveal Universal and Tissue-Specific Mutagenic Mechanisms Operating in the Human Body.

Somatic mutations are inevitable in human genomes and can lead to tumorigenesis, yet baseline mutagenesis in non-cancerous normal cells remain poorly understood. Here, we analyzed the mutation profiles of 11,949 normal samples across 25 tissues obtained from whole-genome and whole-exome sequencing datasets. We applied stringent statistical hypothesis for detecting enrichment and enrichment-adjusted Minimal Estimate of Mutation Load (MEML) in trinucleotide motifs preferred by known mutagenic processes. We found several cancer-associated mutational motifs in cancer-free tissues. Samples enriched with C→T mutations in nCg motif associated with clock-like spontaneous meCpG deamination were detected across all tissues. We revealed another clock-like motif, T→C substitutions in aTn motif associated with exposure to small epoxides and other SN2 electrophiles, in several tissues. Donors with several non-cancerous diseases showed significantly higher, age-independent, and concordant accumulation of aTn and nCg motifs compared to healthy donors. Motifs associated with chemical exposures showed sporadic, tissue and disease-specific mutagenesis. APOBEC-induced C→T and C→G mutations in tCw motif were enriched in bladder, lung, small intestine, liver, and breast with preference for APOBEC3A-like mutagenesis in most. Together, our analyses elucidated several ongoing mutagenic processes in normal human tissues and provided a robust analytical framework for identifying mutagenic sources from somatic mutation catalogues.

Journal Article↗

PubMed2026

Anatomical location defines distinct molecular subtypes of mucosal melanoma.

BACKGROUND: Mucosal melanoma (MM) is a rare and aggressive melanoma subtype that is understudied. The relationships between anatomical location, genomic alterations, stage at presentation, and survival remain incompletely characterized. METHODS: We carried out a retrospective single tertiary center study of 105 patients with histologically confirmed MM diagnosed between 1996 and 2025. Clinical and genomic data were analyzed to evaluate associations between anatomical location, mutational profile, stage at presentation, and survival outcomes, including melanoma-specific mortality. RESULTS: Lower-body tumors arising in the anus or genital areas were enriched for KIT and splicing factor 3 subunit B1 alterations, whereas NRAS mutations were distributed across anatomical regions. Among the two most common mutated genes, NRAS-mutant tumors were more likely than KIT-mutant tumors to present with metastatic disease [53% versus 19%; P = 0.046, odds ratio (OR) 4.7, 95% confidence interval (CI) 1.15-19.41]. Lower-body tumors were associated with worse overall survival (OS) than upper-body tumors (median 2.81 versus 8.40 years; OR = 0.05) and with higher melanoma-specific mortality. In multivariable analyses, upper-body location remained independently associated with improved OS (hazard ratio 0.14, 95% CI 0.05-0.36, P < 0.001). CONCLUSIONS: Anatomical location of MMs and genomic alterations define biologically and clinically distinct subtypes.

KIT mutation↗

PubMed2024

Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach.

Biological mechanisms related to cancer development can leave distinct molecular fingerprints in tumours. By leveraging multi-omics and epidemiological information, we can unveil relationships between carcinogenesis processes that would otherwise remain hidden. Our integrative analysis of DNA methylome, transcriptome, and somatic mutation profiles of kidney tumours linked ageing, epithelial-mesenchymal transition (EMT), and xenobiotic metabolism to kidney carcinogenesis. Ageing process was represented by associations with cellular mitotic clocks such as epiTOC2, SBS1, telomere length, and PBRM1 and SETD2 mutations, which ticked faster as tumours progressed. We identified a relationship between BAP1 driver mutations and the epigenetic upregulation of EMT genes (IL20RB and WT1), correlating with increased tumour immune infiltration, advanced stage, and poorer patient survival. We also observed an interaction between epigenetic silencing of the xenobiotic metabolism gene GSTP1 and tobacco use, suggesting a link to genotoxic effects and impaired xenobiotic metabolism. Our pan-cancer analysis showed these relationships in other tumour types. Our study enhances the understanding of kidney carcinogenesis and its relation to risk factors and progression, with implications for other tumour types.

Kidney Neoplasms↗

PubMed2026

Sodium Overload-Related Molecular Subtypes and a Four-Gene Prognostic Signature Predict Survival, Immune Landscape, and Therapeutic Response in Acute Myeloid Leukemia.

Sodium overload has recently emerged as a critical metabolic stressor involved in cancer progression; however, its molecular characteristics and clinical relevance in acute myeloid leukemia (AML) remain unexplored. RNA-seq data sets, clinical annotations, and mutational profiles of AML patients were annotations from The Cancer Genome Atlas and integrated with Genotype-Tissue Expression normal samples. Sodium overload-related genes (SORGs) were obtained from GeneCards. Differentially expressed SORGs (DESORGs) screened by applying the limma statistical model, followed by univariate Cox proportional hazards regression, consensus clustering, functional enrichment, immune infiltration analysis, and pathway evaluation. A prognostic signature was developed through least absolute shrinkage and selection operator regression followed by multivariate Cox modeling. The model's performance was further verified in two external GEO data sets (GSE71014 and GSE37642). Nomogram construction, subgroup analysis, tumor mutational burden (TMB) assessment, drug sensitivity prediction, transcription factor (TF) analysis, and competing endogenous RNA (ceRNA) network analyses were also performed. A total of 57 DESORGs were identified, and 2 sodium overload-related molecular subtypes exhibited distinct survival, immune infiltration, and inflammatory pathway activation. A robust four-gene signature (DOCK1, GABRE, HTR7, ACSM1) stratified patients into high- and low-risk categories with significantly different survival across training and validation cohorts. High-risk patients displayed increased immune infiltration, higher TMB, reduced sensitivity to multiple chemotherapeutic drugs, and inferior predicted response to PD-L1 blockade. TF and ceRNA networks revealed multilayered transcriptional and post-transcriptional regulation of the signature genes. This study identifies sodium overload-related molecular heterogeneity in AML and establishes a validated four-gene prognostic signature that integrates genomic, immunologic, and therapeutic features, offering potential utility for personalized risk assessment and treatment optimization.

Humans↗

PubMed2025

Quantifying the mutational landscape of retroviral and lentiviral vectors in gene therapy patients.

Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is a monogenic disorder caused by mutations in the ADA gene. Gene therapy using γ-retroviral and lentiviral vector gene addition approaches have shown curative results. We sequenced the ADA transgene in transduced CD3+ T cells, and in peripheral blood cells from patients treated with autologous CD34+ cells transduced with either a γ-retroviral or lentiviral ADA gene vector to assess transgene mutational profiles. In both CD3+ T cells and ADA-SCID patients' cells treated with the lentiviral vector, we observed significantly higher occurrences of guanine (G)-to-adenosine (A) base substitutions than with the γ-retroviral vector. We hypothesized that this G-to-A mutational signature was due to the APOBEC3 cytosine deaminase protein family. By knocking out APOBEC3 genes in HEK239T packaging cells, APOBEC3-mediated mutagenesis decreased by 91.2% along the transgene in CD34+ transduced cells in comparison to CD34+ cells transduced with lentiviral supernatant packaged in parental HEK293T cells.

Humans↗

PubMed2025

Population-Specific Immunogenomic Alterations in Gallbladder Cancer and Prognostic Significance.

Gallbladder carcinoma is a deadly disease with a poor prognosis, and recent clinical data suggest only a modest benefit of PD1/PDL1 inhibitors in this disease. Optimizing immunotherapeutic approaches will require a detailed understanding of the immunogenomic landscape of this disease worldwide. We combined targeted next-generation sequencing and immunohistochemistry to create detailed immunogenomic landscapes from 2 cohorts of gallbladder cancer cases from the United States (n = 60) and Chile (n = 62). Mutations in TP53, SMAD4, KRAS, PIK3CA, ARID2, ARID1A, ATM, FBXW7, ERBB2, and NF1 were found in both the US and Chilean primary cohorts, as well as amplifications in ERBB2, CCNE1, MDM2/CDK4, and CCND1. Despite similar mutation profiles, the immune profiles were distinct, with the Latin American cohort having higher densities of biomarkers associated with CD4+ T cells and PD-1 but lower densities of CD68+ macrophages compared with the North American cohort. Clustering and correlation analyses suggest novel immune subgroups and clinical associations independently of any specific mutations. Additionally, supported by multiplexed single-cell imaging technology, we identified low CD4 and high V-domain Ig suppressor of T cell activation as a candidate biomarker pair of poor outcomes. In summary, our findings highlight the importance of sensitivity to geographic location when considering therapeutic developments and pave a path for further immune investigations of this understudied disease.

Humans↗

PubMed2026

Liquid biopsy: a new window on the BRCA genes.

The Breast Cancer Susceptibility Gene (BRCA)-associated tumors represent a constantly evolving and intriguing scenario in oncology, in which the availability of novel systemic treatment, mainly including the poly (ADP-ribose) polymerase (PARP) inhibitors, has enabled an improved survival benefit in clinical subgroups. The expanding regulatory approvals of PARP inhibitors have inevitably reshaped the clinical indications for BRCA testing, moving the BRCA1/2 profiling from the traditional and preventive workflows to therapeutic paths. Despite advances in technology and treatment, substantial limitations remain in current genetic and genomic tools for the detection of deleterious BRCA1/2 variants. Germline and tumor tissue testing provide only a snapshot of a patient's disease, failing to capture the dynamic and longitudinal aspects of tumor clonal evolution. In this scenario, liquid biopsy (LB) profiling of BRCA1/2 genes, primarily as circulating tumor DNA, represents a highly active area of research potentially affecting many aspects of cancer screening, diagnosis, and monitoring in individuals who are carriers of BRCA1/2 deleterious variants. Beyond the attractive potential to surrogate the tumor tissue testing, to overcome the cancer spatial and temporal heterogeneity, and to monitor the tumor mutational profile over time, accurately detecting all clinically relevant BRCA genetic variants and epigenetic modifications using LB remains technically challenging.

BRCA1/2↗

PubMed2026

CCT2 defines a highly cisplatin-resistant and poor-prognosis subtype of lung adenocarcinoma.

Cisplatin-based chemotherapy is a standard treatment for lung adenocarcinoma (LUAD), yet acquired cisplatin resistance remains a marked cause of treatment failure. The molecular mechanisms driving cisplatin resistance in LUAD have not been fully elucidated. The present study integrated bulk transcriptomic data, genomic mutation profiles and single-cell RNA sequencing data to systematically investigate cisplatin resistance in LUAD. Resistance-associated genes were identified through differential expression, survival analysis and database integration. Unsupervised clustering was used to define cisplatin resistance-associated subtypes. Functional characteristics were explored using pathway enrichment, immune infiltration, tumor mutation burden and weighted gene co-expression network analysis. A machine learning framework incorporating 101 algorithms was applied to identify key genes and construct a prognostic model. Single-cell analyses and in vitro experiments were performed to validate the biological role of the core gene. Molecular docking and molecular dynamics simulations were conducted to identify potential therapeutic compounds. A total of two molecular subtypes with distinct cisplatin resistance levels and prognostic outcomes were identified. The high-resistance subtype exhibited enhanced cell cycle activity, DNA repair signaling and immune heterogeneity. Machine learning analysis revealed a five-gene signature, with chaperonin-containing TCP1 subunit 2 (CCT2) emerging as a key regulator of cisplatin resistance. Single-cell analyses showed that CCT2 was predominantly enriched in resistant epithelial cell subpopulations. Functional experiments demonstrated that CCT2 knockdown significantly inhibited cell proliferation and enhanced cisplatin sensitivity in LUAD cell lines. A number of candidate compounds targeting CCT2 exhibited stable binding in silico. The present findings identified CCT2 as a key mediator of cisplatin resistance in LUAD and provided potential therapeutic strategies to overcome chemotherapy resistance.

chaperonin-containing TCP-1 subunit 2↗

PubMed2026

Associations of neighborhood deprivation with breast cancer tumor genomics, targeted treatment use, and survival.

PURPOSE: Neighborhood environments appear to influence breast cancer biology and outcomes. This study evaluated somatic, treatment, and outcome differences by Area Deprivation Index in patients with metastatic breast cancer. METHODS: Retrospective, population-based cohort study using clinical and genomic data gathered between 2015 and 2024 at four academic institutions in the United States. The outcomes were differences in circulating tumor DNA mutation profiles, PI3K inhibitor use, and survival between patients with metastatic breast cancer living in high deprivation (Area Deprivation Index ≥ 60 by national rank) and low deprivation (< 60) neighborhoods. RESULTS: Among 1127 patients with metastatic breast cancer, 335 (29.7%) lived in high deprivation areas. These patients were more likely to have TP53 mutations (Odds ratio 1.49, 95% Confidence Interval 1.07-2.08, P = 0.018). Among hormone receptor-positive, HER2-negative patients eligible for PI3K inhibitors, those from high deprivation areas were less likely to receive them (17.4% vs. 36.7%, p = 0.02). Median survival from the time of circulating tumor DNA testing was significantly shorter in the high deprivation group (24 months versus 28 months, p = 0.04) and for Black patients in the high deprivation group versus Black patients in low deprivation group and all White patients (15 months versus 25-28 months, p = 0.02). CONCLUSIONS: We found that patients with metastatic breast cancer living in high deprivation neighborhoods were more likely to have TP53 mutations, an indicator of aggressive disease biology, less likely to receive PI3K inhibitors, and had shorter overall survival compared to patients living in low deprivation neighborhoods by Area Deprivation Index.

Humans↗

PubMed2025

HER2 alterations across solid tumors: implications for comprehensive testing.

PURPOSE: ERBB2 (HER2) alterations (eg, overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial. METHODS: HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association. RESULTS: Of the 653 cases, HER2 IHC scores were distributed as 3+ (3.1%), 2+ (13.2%), and 1+ (19.8%), with 63.9% being IHC-negative. ERBB2 CN amplification was observed in 3.1%, with 75% exhibiting IHC3+. Pathogenic mutations were found in 3.1%, with low IHC3+ rates (5%). Among samples with ERBB2 mutations, only 3 had CN amplifications (1-positive, 2-intermediate). Somers'-D analysis revealed a strong association between CNV and IHC expression (D = 0.73, P < .001). CONCLUSION: This study highlights ERBB2 alterations across diverse cancers, demonstrating their heterogeneity and clinical significance. ERBB2 mutation-carrying tumors are less likely to have HER2 protein 3+ expression or CN amplification, indicating the need for comprehensive genomic analysis to identify those patients. In the context of pan-tumor approval of T-DXd for HER2, findings support integrating genomic and phenotypic data to enhance diagnostic precision and inform therapeutic decision-making. Comprehensive ERBB2 (HER2) testing across tumor types is essential to expand access to HER2-targeted therapies.

Humans↗

PubMed1990

Mutational analysis of the H-ras oncogene in spontaneous C57BL/6 x C3H/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens.

The frequency and mutational profile of H-ras gene activation were determined in spontaneous liver tumors of male C57BL/6 x C3H/He mice and in tumors induced with the genotoxic hepatocarcinogen benzidine.2 HCl or the nongenotoxic hepatocarcinogens phenobarbital, chloroform, and ciprofibrate. DNA sequence analysis of the H-ras gene from representative tumors revealed that 32 of 50 (64%) spontaneous tumors and 13 of 22 (59%) benzidine.2 HCl-induced tumors contained a point mutation in codon 61. Tumors induced with the nongenotoxic agents had a much lower frequency of codon 61 mutations, i.e., phenobarbital, 1 of 15 (7%); chloroform, 5 of 24 (21%), and ciprofibrate, 8 of 39 (21%). No mutations were observed at codons 12, 13, and 117 in tumors from any of the groups. Only three base pair substitutions within codon 61 were found. The one most frequently detected in all of the groups was a C.G to A.T transversion at the first nucleotide position, occurring at a 59%, 85%, 100%, 80%, and 88% frequency in the spontaneous tumors and in the tumors induced with benzidine 2.Hcl, phenobarbital, chloroform, and ciprofibrate, respectively. In these same groups an A.T to G.C transition or an A.T to T.A transversion at the second nucleotide position occurred at a frequency of 34%, 8%, 0%, 0%, and 12%, and 6%, 8%, 0%, 20%, and 0%, respectively. The number of tumors carrying an activated H-ras gene in the nongenotoxic treatment groups is within the range that would be expected if those animals had not received any treatment. This indicates that the activation of the H-ras gene in those tumors is probably the result of a spontaneous event. The data suggest that these toxicologically and pharmacologically diverse nongenotoxic hepatocarcinogens increase the frequency of liver tumors but do not induce mutations in the H-ras gene. Instead these agents appear to interact with a population of cells that do not contain an activated H-ras gene. This suggests that the mechanisms of tumor development by these nongenotoxic carcinogens differ at least partially from the mechanisms responsible for the development of spontaneous tumors or those induced by a typical genotoxic agent.

Animals↗

PubMed2026

Clinical and genomic characterization of Influenza A co-infection with SARS-CoV-2 and Influenza B: a respiratory surveillance study in Assam, India.

Influenza and SARS-CoV-2 are the primary contributors to seasonal respiratory infections and frequently co-circulate, creating significant health challenges. The present respiratory surveillance study was conducted in Dibrugarh, Assam, India from January 2025 to August 2025 to investigate the genomic characteristics of circulating viruses and identify potential co-infections. Overall, 4,948 respiratory samples were screened using multiplex real-time PCR, followed by subtyping of Influenza A and Influenza B. Next-generation sequencing (NGS) was performed in selected positives of SARS-CoV-2 and Influenza A. Genomic analysis included mutational profiling, phylogenetic analysis and N-glycosylation site prediction using bioinformatics tools. Two co-infection cases were detected: one involving Influenza A (H3N2) with SARS-CoV-2 (Omicron XFG lineage) and another involving Influenza A (H3N2) with Influenza B (Victoria lineage). Both patients experienced mild illness without hospitalisation. NGS revealed that the Influenza A (H3N2) viruses belonged to clade 3C.2a1b.2a.2a.3a.1 while SARS-CoV-2 sequence was classified under the Omicron XFG lineage. Mutational analysis of the HA gene showed several amino acid differences compared to the reference vaccine strain A/Darwin/6/2021. N-glycosylation analysis predicted conserved sites at positions 79, 181, 262, and 301 in all strains along with an additional predicted site at position 110 in both co-infection cases. Although the co-infection cases presented with mild clinical manifestations, the observed genomic variations indicate a potential role of co-infecting viruses in shaping viral evolution. Given the limited genomic data available from Northeast India, the study underscores the need for sustained large scale follow up and genomic surveillance to monitor emerging mutations and target future vaccine strategies.

Humans↗

PubMed2026

Genomic Epidemiology and Clinical Characteristics of Mpox Lineage C.1 Outbreak in Thailand, 2023-2024.

Since 2022, human monkeypox virus (hMPXV) has emerged in non-endemic regions, including Thailand. However, the genomic dynamics and clinical correlates of local transmission remain incompletely defined. Whole-genome sequencing was performed on hMPXV from 16 patients in Thailand (2023-2024) using targeted amplicon NGS. Phylogenetic analyses integrated global reference sequences. Mutational profiles, specifically non-synonymous substitutions and APOBEC3-associated signatures, were analyzed in relation to clinical data. Phylogenetic reconstruction identified three temporal phases. Early 2022 cases (clade IIb lineages A and B) were interspersed with global sequences, consistent with multiple introductions. In contrast, 2023-2024 cases were dominated by lineage C.1. All 16 genomes belonged to C.1 (one C.1.1), and formed a distinct mid-2023 cluster, designated C.1/Thai/Cluster, supporting sustained local transmission. APOBEC3-associated mutations were pervasive across the C.1 lineage overall, including within C.1/Thai/Cluster, without evidence of significant enrichment specific to this cluster. The cohort comprised exclusively male patients (81% HIV-positive, MSM), with predominantly genital painful lesions and a median recovery time of 23 days. No significant associations were detected between viral genetic variation and clinical outcomes. Mpox transmission in Thailand evolved from multiple introductions to sustained C.1-dominated local spread, underscoring the importance of continued genomic surveillance.

Humans↗