Mammalian Genome最新文献

{"title":"Tracing the genetic legacy of Malabari goats through complete mitogenome sequencing: evidence of maritime exchange via the historic spice route.","authors":"M R Akhila, Marykutty Thomas, Jinty Sukumaran, P M Rojan, J Saalom King, R Thirupathy Venkatachalapathy, K A Bindu","doi":"10.1007/s00335-026-10269-6","DOIUrl":"10.1007/s00335-026-10269-6","url":null,"abstract":"<p><p>The Malabari goat of South India is one of the most efficient dual-purpose breeds, exhibiting exceptional adaptability to humid tropical stressors. This study aimed to characterize the complete mitochondrial genome of Malabari goats and to decipher their maternal phylogenetic relationships, thereby providing insights into lineage divergence, domestication origins and genetic connectivity with global caprine populations. Whole-genome sequencing of pooled DNA from 20 unrelated Malabari goats revealed a complete mitogenome comprising 37 genes, including 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs) and two ribosomal RNAs (rRNAs), in addition to a hypervariable non-coding displacement loop (D-loop) region. A total of 45 single nucleotide polymorphisms (SNPs) and two indels were identified, of which 21 SNPs were detected in PCGs-six of them non-synonymous. Importantly, we report the first tRNA mutation described in goats: a novel heteroplasmic substitution (11693 T>C) in the MT-TL2 gene coding for tRNA^LeuCUN. The mitochondrial genome analysis of Malabari goats revealed their closest genetic affinity with Iraqi Meriz goats and Arabian goat populations, highlighting significant maternal contributions via ancient maritime trade networks, distinct from most Indian breeds that predominantly belong to haplogroup A. The whole mitogenome phylogenetic analysis revealed that Malabari goats cluster in a monophyletic group together with local goats from Vietnam, domestic goats from Malaysia and domestic goats from Russia. Phylogenetic reconstruction based on mitochondrial D-loop placed Malabari goats within haplogroup B1 along with goats from Iraq, Oman and Gujarat in India. Mitogenome analysis of Malabari goats provides genetic evidence of their genetic roots shaped by maritime exchanges along the ancient Spice Route.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a metastasis-associated prognostic gene signature in osteosarcoma through integrated bioinformatics and functional analysis.","authors":"Qingquan Xia, Xiangchao Meng, Xuhua Wu, Xujun Li, Teng Fei, Ke Rong","doi":"10.1007/s00335-026-10272-x","DOIUrl":"10.1007/s00335-026-10272-x","url":null,"abstract":"<p><p>Osteosarcoma is a highly aggressive bone malignancy with a strong tendency for metastasis and poor clinical outcomes. The molecular mechanisms driving osteosarcoma progression and metastasis remain incompletely understood, highlighting the need to identify robust biomarkers and therapeutic targets. Weighted gene co-expression network analysis (WGCNA) was performed using osteosarcoma datasets from the Gene Expression Omnibus to identify metastasis-associated gene modules and hub genes. Expression, methylation, mutation, immune infiltration, and drug sensitivity analyses were conducted using multiple public databases, including TCGA, GSCA, UALCAN, and cBioPortal. A prognostic model was developed using the TARGET osteosarcoma cohort and validated in an independent GEO dataset. Functional roles of hub genes were investigated through loss- and gain-of-function experiments in sarcoma cell lines using RT-qPCR, Western blotting, proliferation, colony formation, wound-healing, and luciferase reporter assays. Four hub genes, AURKB, CDC20, KIF11, and TOP2A, were identified as strongly associated with metastasis. These genes were significantly upregulated in sarcoma tissues and cell lines and demonstrated excellent diagnostic performance. Promoter hypomethylation and frequent genomic alterations contributed to their aberrant expression. High expression of the hub genes was associated with poor overall survival, and a four-gene prognostic model showed strong predictive performance in both training and validation cohorts. Functional assays confirmed that these genes promote sarcoma cell proliferation and migration, while miRNA-mediated regulation and drug resistance associations further highlighted their biological relevance. This integrated computational and experimental study identifies AURKB, CDC20, KIF11, and TOP2A as key oncogenic drivers in osteosarcoma, with significant diagnostic, prognostic, and therapeutic implications.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of auditory and vestibular function and gene therapy in the Snell's waltzer mouse model of human deafness and balance dysfunction.","authors":"Eyal Marton, Roni Hahn, Lior Bikovski, Gwenaëlle S G Géléoc, Jeffrey R Holt, Matti Mintz, Karen B Avraham","doi":"10.1007/s00335-026-10263-y","DOIUrl":"10.1007/s00335-026-10263-y","url":null,"abstract":"<p><p>The Snell's waltzer mouse (Myo6^sv/sv) serves as a model for human deafness and vestibular behavioral impairment, caused by a spontaneous 130 bp recessive deletion in the Myo6 gene. In this study, we characterized the auditory and vestibular phenotypes of Myo6^sv/sv mice. These mice exhibit profound hearing loss, with cochlear hair cell stereocilia beginning to fuse soon after birth, ultimately leading to disorganization of hair bundles and degeneration of hair cells. Mice also exhibit behavioral phenotypes characterized by severe imbalance, hyperactivity with bouts of circling, and delayed spatial learning of a novel environment, but preserved normal behavioral circadian rhythms. These behaviors emerge in association with the loss of the characteristic staircase morphology of vestibular hair cell stereocilia soon after birth and the subsequent profound elongation of the stereocilia. Adeno-associated virus (AAV) gene replacement therapy, delivered on the day of birth or one day after, failed to restore auditory or vestibular function. Our findings underscore the essential role of Myo6 in the auditory and vestibular systems and imply prenatal intervention may be required for effective therapy.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics integration and machine learning define an iron-sulfur cluster/zinc-binding protein prognostic signature in esophageal squamous cell carcinoma.","authors":"Wenhuan Chen, Tongtong Chen, Zhixuan Li, Wan Lin, Zefeng Xie, Hansheng Wu, Liyan Xu, Enmin Li, Hefeng Zhang, Yinwei Cheng","doi":"10.1007/s00335-026-10270-z","DOIUrl":"10.1007/s00335-026-10270-z","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is characterized by substantial intratumoral heterogeneity and poor clinical prognosis. Although metalloproteins are well-documented to drive ESCC malignant progression, incomplete functional annotation of this protein family significantly impedes the clinical translation of related research outcomes. This study reports the development and validation of a reliable prognostic model via integrating AlphaFold2-predicted iron-Sulfur (Fe-S) Cluster/Zinc (Zn)-binding proteins with ESCC multi-omics data. Nine differentially expressed AlphaFold2-predicted Fe-S/Zn-binding proteins significantly associated with ESCC prognosis were identified through integrated analysis of multi-omics and clinical data from public datasets and independent ESCC cohorts. After systematic evaluation of 117 machine learning combinations, a three-Fe-S/Zn-binding protein Prognostic Signature (FZPS) comprising YPEL5, MIB1 and ELAC2 was constructed, and validated as an independent predictor of poor overall survival across cohorts. High FZPS risk correlates with an immune-excluded, stress-adaptive phenotype with p21-driven inflammation and intrinsic immunotherapy resistance, while low-FZPS tumors harbor more actionable mutations and exhibit enhanced sensitivity to targeted therapy and immunotherapy. In vitro assays confirmed YPEL5 knockdown markedly suppresses ESCC cell viability, proliferation and migration. In conclusion, FZPS is a reliable independent prognostic biomarker guiding precision oncology practice for ESCC.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide characterization of copy number variations in Nagami Mithun (Bos frontalis) using whole-genome resequencing.","authors":"Bendangkokba Kichu, Harshit Kumar, Rajkrishna Mondal, Kuluve Chotso, J K Chamuah, S S Hanah, Girish Patil Shivanagowda","doi":"10.1007/s00335-026-10268-7","DOIUrl":"10.1007/s00335-026-10268-7","url":null,"abstract":"<p><p>Copy number variations (CNVs) represent an important source of structural genomic variation contributing to genomic diversity in livestock species. The Nagami Mithun (Bos frontalis), a semi-domesticated bovid indigenous to the forested hill regions of Northeast India, remains poorly characterized at the level of genome structural variation. In this study, whole-genome resequencing data from 12 Nagami Mithun individuals were analyzed to establish the first genome-wide copy number variation (CNV) map for this indigenous population. After quality filtering and alignment to the Bos taurus ARS-UCD2.0 reference genome, CNVs were detected using the read-depth-based tool CNVnator v0.4.1 with stringent filtering criteria (e-value < 0.05, q0 < 0.5, length > 1 kb). A total of 7273 CNVs were identified, including 5005 deletions (68.8%) and 2,268 duplications (31.2%), which were subsequently integrated into 1135 CNV regions (CNVRs). Population-level integration of individual CNVs resulted in 1135 CNVRs spanning approximately 173.4 Mb of the autosomal genome. Functional annotations identified 2281 genes overlapping CNVRs. Gene Ontology enrichment analysis identified overrepresentation of genes annotated to chemosensory perception, immune-related processes, and amino-acid transport functions, while KEGG pathway analysis identified enrichment of pathways annotated as natural killer cell-mediated cytotoxicity and antigen processing and presentation. CNV-QTL overlap analysis identified hypothesis-generating candidate genomic regions harboring genes (e.g., AFF2, EDA, COL4A5, TRPC5) that are associated with production, reproduction, and conformation traits in bovines, representing putative positional overlaps requiring future validation in Mithun populations. This study provides a foundational structural variation resource for future comparative, conservation, and functional genomic studies in Mithun. These findings provide a valuable genomic resource for future marker-assisted selection, comparative genomics, and conservation breeding programs aimed at preserving Nagami Mithun populations.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZDHHC5 may regulate the function of NKT cells and the immune response in Meniere's disease.","authors":"Ruilong Li, Keguang Chen","doi":"10.1007/s00335-026-10264-x","DOIUrl":"https://doi.org/10.1007/s00335-026-10264-x","url":null,"abstract":"<p><p>Meniere's disease (MD) is a heterogeneous, rare inner ear disorder characterized by recurrent vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural fullness. Its molecular mechanisms remain unclear due to significant clinical and immunological heterogeneity. In this study, we integrated multi‑omics genetic data to systematically screen for palmitoylation regulatory genes associated with MD risk. We first intersected 31 core palmitoylation genes with blood cis‑eQTL datasets to identify candidate expression‑related genes, then performed two‑sample Mendelian randomization (MR) to examine their genetic correlation with MD. Summary‑data‑based MR (SMR) using two independent peripheral blood eQTL cohorts (eQTLGen and GTEx) was further applied to validate robust candidate genes. Two‑sample inverse‑variance weighted (IVW) MR revealed nominally significant associations between PPT2, ZDHHC18, ZDHHC5 and MD risk. Independent SMR validation confirmed that peripheral ZDHHC5 expression was significantly correlated with MD (eQTLGen: PSMR = 0.023; GTEx: PSMR = 0.006), and a non‑significant HEIDI test ruled out strong linkage disequilibrium confounding. We further explored potential immune mediators using a two‑step MR screening framework covering 731 peripheral immune cell phenotypes. After Benjamini-Hochberg false discovery rate (FDR) correction for all immune traits to control for multiple testing, no immune cell phenotype retained an FDR < 0.05 association with MD; therefore, formal mediation analysis was not conducted. In summary, this MR‑based genetic analysis identifies ZDHHC5 as a gene associated with MD susceptibility. The potential immune regulatory axis involving NKT cells remains speculative and requires validation through large‑scale stratified immune cohort data and functional cellular/animal experiments. No definitive causal or therapeutic conclusions can be drawn from the present genetic statistical evidence alone.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening for candidate genes and cell populations associated with atherosclerotic calcification using single-cell RNA sequencing.","authors":"Huai Wu Yuan, Weiye Wang, Wei Cheng, Hongzhe Wang, Boyan Song, Tian Xiang Chen, Guo Ping Peng","doi":"10.1007/s00335-026-10262-z","DOIUrl":"10.1007/s00335-026-10262-z","url":null,"abstract":"<p><p>Calcification often occurs as a characteristic pathological manifestation in the progression of atherosclerosis (AS) plaques, but its mechanism is not fully understood yet. The purpose of this research was to supplement the exploration of key candidate genes and key cells involved in the calcification process of AS, building on existing insights into its underlying mechanisms. Through the examination of our internally generated single‑cell RNA sequencing (scRNA-seq) dataset derived from human carotid plaque samples, pivotal cellular populations associated with AS calcification were successfully identified. Following this identification, a comprehensive analytical approach was employed, incorporating differential gene expression profiling alongside the establishment of protein-protein interaction (PPI) networks, thereby enabling the extraction of critical genetic markers within these cellular subsets. Furthermore, a molecular regulatory framework was assembled, aiming to elucidate the mechanistic pathways through which these genetic determinants contribute to the calcification phenomena in AS pathology. Moreover, analysis of cell communication was applied to explore the interactions among cells. Pseudo-time analysis was employed to explore the expression of key candidate genes during the differentiation of key cells. Finally, monocytes were identified as key cells. WARS1, IFITM1, ANXA1, ADGRE2, and S100P were identified as key candidate genes. Moreover, 115 transcription factors such as THRB and 118 miRNAs such as hsa-miR-196a-5p were predicted to be associated with the key candidate genes. Across both calcified and non-calcified control specimens, the cellular communication between endothelial cells and natural killer (NK) T cell populations was consistently orchestrated via the PPBP-CXCR2 signaling axis. During monocytic differentiation trajectories, ADGRE2 expression exhibited a biphasic pattern characterized by initial gradual elevation followed by subsequent decline. Conversely, both ANXA1 and S100P demonstrated progressive upregulation throughout the differentiation process. The expression of IFITM1 and WARS1 first decreased, then increased, and finally decreased again. The present investigation successfully pinpointed five critical genes alongside one key cellular population, collectively providing potential molecular insights and candidate targets for further investigation into AS calcification.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide meta-analysis with 1,590,596 individuals identifies 12 novel risk loci for systemic lupus erythematosus.","authors":"Gaizhi Zhu, Wenting Su, Jiahui Deng, Bing Zhai, Ran Gao, Jinming Qiu, Keqi Gu, Ziqing Bian, He Xiao, Guoming Luan, Renxi Wang","doi":"10.1007/s00335-026-10266-9","DOIUrl":"10.1007/s00335-026-10266-9","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a chronic life-threatening and relapsing-remitting multisystem autoimmune disease. However, the genetic susceptibility of SLE has not been fully elucidated. This study will explore the genetic risk loci of SLE. We performed the larger multi-ancestry meta-analysis of genome-wide association study (GWAS) including 22,494 cases with SLE and 1,568,102 healthy controls. Multi-ancestry meta-analysis identified 101 risk loci including 12 novel loci. Across 101 loci, 2,209 likely causal genes are indicated and 265 genes are prioritized, based on eight biological prioritization criteria. The most significantly locus were located on 6p21.32, whereas the highest-ranked candidate causal gene was BLK. Heritability analyses demonstrated a liability scale of the heritability is 25.49%, whereas an estimated 1.25 million effective sample sizes would be necessary to explain 90% of phenotypic variance. Gene enrichment, gene-set analyses, and the genetic correlation revealed that SLE-related genes were enriched in whole blood and spleen, promoted MHCII-related pathways, JAK-STAT signaling, abnormal activation of T and B cells, autoantibodies such as anti-nuclear antibody and anti-neutrophil antibody production, and had a positive genetic correlation with autoimmune diseases (e.g., rheumatoid arthritis), mental and neurological disorders (e.g., schizophrenia), and cardiovascular diseases (e.g., hypertension). Finally, druggable, gene-drug interaction, drug target, and drug repurposing analysis suggested some potential targets (e.g., BLK) and drug (e.g., riboflavin) repurposing for SLE. In conclusion, we identified 101 risk loci including 12 novel loci for SLE. Based on 101 loci, we provided new biological insights, some potential targets, and drug repurposing for SLE.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future objectives of the International Mouse Phenotyping Consortium (IMPC): functional evaluation of human disease-relevant cis-regulatory elements in the mouse genome.","authors":"Naoki Kubo, Akiko Oguchi, Hiroshi Masuya, Takanori Amano, Akihiko Sakashita, Hideya Kawaji, Takeya Kasukawa, Shinya Oki, Shinya Ayabe, Toyoyuki Takada, Atsuo Ogura, Kimiko Inoue, Yasuhiro Murakawa, Masaru Tamura, Atsushi Yoshiki, Toshihiko Shiroishi","doi":"10.1007/s00335-026-10258-9","DOIUrl":"10.1007/s00335-026-10258-9","url":null,"abstract":"<p><p>The International Mouse Phenotyping Consortium (IMPC) has established a large-scale functional genomics resource by systematically generating and phenotyping knockout mouse lines, linking gene function to mammalian phenotypes. However, interpreting disease-associated non-coding variants remains particularly challenging due to their abundance, context-dependent activity, and the complexity of gene regulation. Genome-wide association studies (GWAS) have shown that many disease-associated loci map to non-coding regions. In addition, recent large-scale consortia have catalogued millions of candidate cis-regulatory elements (CREs) across mammalian genomes; however, predicting which elements contribute to disease-relevant gene regulation and organismal phenotypes remains difficult. Together, these observations highlight disease-relevant CREs as an important but still underexplored component of human disease mechanisms. In this white paper, we outline strategies to address this challenge: (i) prioritization of disease-relevant candidate CREs, (ii) genome editing in mice to functionally evaluate CREs, and (iii) the establishment of interdisciplinary working groups. By extending its activities beyond protein-coding sequences, the IMPC has a unique opportunity to define the functional and phenotypic impact of disease-relevant CREs in vivo at scale, thereby improving our understanding of how non-coding regulatory elements contribute to mammalian phenotypes and human disease.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of HLTF context-dependent regulation across TCGA cohorts revealed its potential as new biomarker in tumour.","authors":"Alessia Canevotti, Marija Tursunović, Wendalina Tigani, Graziano Pesole, Matteo Chiara, Matteo De March","doi":"10.1007/s00335-026-10257-w","DOIUrl":"10.1007/s00335-026-10257-w","url":null,"abstract":"<p><p>The SNF2-family Helicase-Like Transcription Factor (HLTF) has been implicated in tumorigenesis, with evidence suggesting both tumour-suppressive and oncogenic functions. To clarify the nature of this increasingly emerging double function, we analysed the full HLTF's alterome across TCGA cohorts combining first gene expression with genomic and epigenomic layers of de-regulation, and investigating further their determinants through the integration of DNA methylation profiles - both at promoter-proximal and distal regions, the copy-number alterations, and all somatic mutations. This multi-layered analysis highlighted specific context-dependent HLTF's regulatory configurations across human cancers, even modulated by either dosage effects or loss-of-function events. The clinical relevance of HLTF's alterations, identified through tumour-specific associations with patient outcomes, supports its potential as new biomarker in cancer overall.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":"37 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13400721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}