Cancer Genetics最新文献

{"title":"Pan-cancer methylation analysis of circulating cell-free DNA","authors":"Wenjiao Dong ,&nbsp;Cia-Hin Lau ,&nbsp;Jiaqi Li ,&nbsp;Zhihao Huang ,&nbsp;Jiahui Li ,&nbsp;Weidong Wu ,&nbsp;Xiaoqing Chen ,&nbsp;Yumei Huang ,&nbsp;Xiaojun Huang ,&nbsp;Meijing Xu ,&nbsp;Haibao Zhu ,&nbsp;Yuanlin Ding","doi":"10.1016/j.cancergen.2025.07.014","DOIUrl":"10.1016/j.cancergen.2025.07.014","url":null,"abstract":"<div><h3>Background</h3><div>Universal cancer screening based on methylation analysis of circulating cell-free DNA (cfDNA) enables multi-organ cancer detection, thereby reducing all-cause mortality and preventing cancer misdiagnosed by guideline-based cancer-specific screening. This study aims to establish a gene methylation panel for blood-based multi-cancer early detection.</div></div><div><h3>Materials and methods</h3><div>Bioinformatics analysis and in-house DNA sequencing of various human cancer cell lines and blood from healthy persons were carried out to identify candidate pan-cancer methylation sites. Methylation-sensitive restriction enzymes-quantitative PCR (MSRE-qPCR) was then used for DNA methylation analysis. Blood cfDNA from 103 patients with diverse cancer types and 40 healthy subjects was extracted for methylation analysis.</div></div><div><h3>Results</h3><div>By bioinformatics analysis and in-house DNA sequencing, we identified two candidates pan-cancer methylation sites, <em>HIST1H4F</em> and <em>CDO1</em>. A long stretch of methylation was found on the promoters of <em>HIST1H4F</em> and <em>CDO1</em> across various cancer cell lines, while these genomic regions are unmethylated in healthy persons. When tested with clinical samples, the detection sensitivity and specificity of our gene methylation panel in detecting pan-cancer were 47.57 % and 90.00 %, respectively. When analyzed by cancer subtypes, the detection sensitivity was the highest in lung cancer (76.92 %), followed by colorectal cancer (63.64 %) and gastric cancer (50.00 %).</div></div><div><h3>Conclusions</h3><div>Our newly established gene methylation panel provides an alternative assay for multi-cancer screening tests. As no bisulfite conversion and invasive procedures are required, it can accelerate cancer diagnosis and streamline the operation for pan-cancer screening.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 182-195"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated m6A modification of pri-miR-93 promotes hepatocellular carcinoma progression via CDKN1A suppression","authors":"Yue Wang ,&nbsp;Xiaorong Zhang ,&nbsp;Fan Yang,&nbsp;Jiaqi Shang,&nbsp;Qing Yang","doi":"10.1016/j.cancergen.2025.06.003","DOIUrl":"10.1016/j.cancergen.2025.06.003","url":null,"abstract":"<div><div>N6-methyladenosine (m⁶A) is the most common RNA modification in eukaryotic transcriptomes and plays a key role in various biological processes. However, its function in disease, particularly in microRNA regulation, remains unclear. Hepatocellular carcinoma (HCC) is a major global health challenge, with high morbidity and mortality rates. Investigating the role of m⁶A modification in HCC may provide valuable insights into its molecular mechanisms.</div><div>This study found that METTL3, an m⁶A methyltransferase, is significantly upregulated in HCC and is associated with poor prognosis. Bioinformatics analysis of the GSE37001 dataset showed that silencing METTL3 in HepG2 cells suppressed cell cycle-related pathways. Among several candidate miRNAs potentially regulated by METTL3 in an m⁶A-dependent manner, miR-93–5p was selected for further study. Experimental results demonstrated that METTL3-mediated m⁶A modification promotes miR-93–5p expression by facilitating pri-miR-93 processing. Functional assays confirmed that miR-93–5p directly targets CDKN1A and downregulates its expression. Moreover, METTL3 overexpression rescued the effects of METTL3 knockdown on pri-miR-93 m⁶A levels and miR-93–5p expression. Rescue experiments further showed that METTL3 promotes HCC cell proliferation and cell cycle progression while inhibiting apoptosis via the miR-93–5p/CDKN1A axis.</div><div>In summary, METTL3 is highly expressed in HCC and contributes to tumor progression by promoting miR-93–5p expression through m⁶A modification, thereby suppressing CDKN1A. These findings highlight a potential regulatory mechanism in HCC and suggest that targeting the METTL3/miR-93–5p/CDKN1A axis could be a novel therapeutic strategy.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 31-40"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated multinodular goiter and follicular adenoma associated with a novel germline DICER1 variant: A benign presentation","authors":"Joshua Chang ,&nbsp;Rachel Rabenn ,&nbsp;Aditi Parikh ,&nbsp;Chen-Han Wilfred Wu","doi":"10.1016/j.cancergen.2025.07.013","DOIUrl":"10.1016/j.cancergen.2025.07.013","url":null,"abstract":"<div><div><em>DICER1</em> syndrome is a tumor-predisposition disorder caused by a germline pathogenic variant in <em>DICER1</em>. Pathogenic variants of <em>DICER1</em> are the monogenic cause of various tumors including pleuropulmonary blastoma (PPB), ovarian sex cord-stromal tumors, and multinodular goiters. We present a family with a novel <em>DICER1</em> pathogenic variant c.5528–2del who presents with development of isolated thyroid goiters/follicular adenoma. A 44 year old female presents with a past medical history of total thyroidectomy along with her 14-year-old son with a past history of multinodular thyroid goiter confirmed as multifocal follicular adenoma with papillary architecture and her 12-year-old daughter with a past history of multinodular thyroid goiter confirmed as diffuse nodular thyroid hyperplasia. No additional <em>DICER1</em> syndrome presentations were observed. A genetics panel revealed that the mother, the 14-year-old son, and the 12-year-old daughter share a heterozygous <em>DICER1</em> c.5528–2del variant, which has not been previously reported. In addition to our direct clinical observations from this family, genetic analysis via in silico prediction models, segregation analysis, and ACMG classification support this variant to be pathogenic. Given the absence of other <em>DICER1</em> syndrome manifestations through human genetics evidence, this variant may be specifically associated with isolated multinodular goiters/follicular adenoma. Our findings contribute to the expanding genotype-phenotype correlation in <em>DICER1</em> syndrome, providing new insights into its variable clinical presentation. Since not all variants are identical, reporting of these observations will advance precision medicine and benefit future patients through more accurate diagnosis, prognosis and personalized management strategies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 200-204"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ADAR1 gene expression and its importance in breast cancer","authors":"Bulent Tekin ,&nbsp;Seda Ekizoglu ,&nbsp;Sare Burcu Kaya ,&nbsp;Mehmet Guven ,&nbsp;Didem Can Trabulus","doi":"10.1016/j.cancergen.2025.06.011","DOIUrl":"10.1016/j.cancergen.2025.06.011","url":null,"abstract":"<div><div>RNA editing mediated by ADAR1 is vital for the survival of mammals, and its malfunction leads to irregular editing of its targets, potentially influencing the observable characteristics of breast cancer. The study aims to investigate ADAR1- p110 and ADAR1-p150 gene expression in breast cancer patients' tissue samples (tumor and normal), to determine the role of this expression in tumor development, and to correlate expression levels with patients' clinical findings to understand breast cancer heterogeneity. In this research, we used tumor and adjacent normal tissue samples from 75 patients diagnosed with breast cancer who had undergone surgery. The levels of gene expression were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study found that ADAR1-p110 expression was significantly higher (1.32-fold, <em>p</em> &lt; 0.0001) in tumor tissue compared to adjacent normal tissue. Similarly, ADAR1-p150 expression also showed a significant increase (1.58-fold, <em>p</em> &lt; 0.0001) in tumor tissue compared to normal tissue. ADAR1-p150 expression was significantly higher in ER (estrogen receptors )-positive patients compared to ER-negative patients (<em>p</em> = 0.04). Additionally, patients with lobular histology showed significantly higher ADAR1-p150 expression levels compared to those with ductal histology (<em>p</em> = 0.02). Our findings, obtained by using tumor and normal tissue from the same individual, demonstrate increased ADAR1 gene expression in tumor tissue. Considering the literature data indicating ADAR1′s association with drug resistance and the correlation we observed between ADAR1 expression levels and certain clinicopathological data of the patients, it is evident that ADAR1 expression is a parameter that should be taken into account in treatment planning.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 106-110"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of VHL variant on multigene panel testing for hereditary breast cancer: Implications for genetic counselling","authors":"Jennifer YM Ling ,&nbsp;Kirk AJ Stephenson ,&nbsp;Tammy L Romanuik ,&nbsp;My Linh Thibodeau ,&nbsp;Maryam Soleimani ,&nbsp;Katherine E Paton","doi":"10.1016/j.cancergen.2025.07.003","DOIUrl":"10.1016/j.cancergen.2025.07.003","url":null,"abstract":"<div><div>As multigene panel genetic testing for hereditary cancer syndromes increases in clinical use, the detection of unexpected secondary findings will occur more commonly. We present the case of a 40-year-old woman with breast cancer who harboured a secondary finding in the <em>VHL</em> gene variant without other cancer risk alleles (e.g., <em>BRCA1/BRCA2</em>) sufficient to explain her primary presentation. Subsequent exam revealed ophthalmic manifestations of von Hippel-Lindau syndrome (VHLS), emphasizing the importance of multidisciplinary clinical assessment and phenotyping. The development of retinal and central nervous system hemangioblastomas, clear cell renal cell carcinomas, pancreatic neuroendocrine tumours and phaeochromocytomas are characteristic of VHLS, but the link with breast cancer is poorly understood. Though the benefit of hereditary cancer genetic testing is well-known, this case highlights the importance of pre-test genetic counselling to prepare patients for all possible results, including additional unanticipated genetic diagnoses. Such pre-test counselling can set appropriate expectations for the possible requirement of ongoing surveillance and/or treatment.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 150-153"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two MLN-TK patients with ETV::ABL1 fusions mediated by different mechanisms with false negative FISH results resolved with RNA fusion analysis","authors":"Patrick Maher ,&nbsp;Tim Jang ,&nbsp;Ruben Ruiz Vega ,&nbsp;Jennifer Miatech ,&nbsp;Gabriela Bastidas Mora ,&nbsp;W.J.R. Quan ,&nbsp;Reeba Prince ,&nbsp;Joanna Chaffin ,&nbsp;Lijun Yang ,&nbsp;Petr Starostik ,&nbsp;Rachel D. Burnside","doi":"10.1016/j.cancergen.2025.06.007","DOIUrl":"10.1016/j.cancergen.2025.06.007","url":null,"abstract":"<div><div>Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusions (MLN-TK) is a newly added entity in the World Health Organization (WHO) 5^th Edition, and within this category, <em>ETV6::ABL1</em> gene fusions are the most commonly reported in the literature. While patients may respond favorably to tyrosine kinase inhibitor (TKI) therapy, prognosis is generally less favorable than for <em>BCR::ABL1</em>-positive chronic myelogenous leukemia (CML), also treated with tyrosine kinase inhibitor therapy (TKIs). We report two patients diagnosed with MLN-TK, both of whom were positive for <em>ETV6::ABL1</em> gene fusions, albeit by different mechanisms but with the same breakpoints. Importantly, one of our subjects also demonstrated <em>BCR::ABL1</em> fusion subclonally to the <em>ETV6::ABL1</em> fusion positive clone. This study emphasizes the importance of resolving false negative and/or discrepant fluorescence in situ hybridization (FISH) results using alternative methods, such as RNA fusion analysis, to aid in the diagnosis of MLN-TK.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 100-105"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and clinical implications of PIK3CA aberrations across cancer types: A real-world next-generation sequencing approach","authors":"Junkyu Kim ,&nbsp;Hye-Lim Jang ,&nbsp;Jung Young Hong ,&nbsp;Seung Tae Kim ,&nbsp;Se Hoon Park ,&nbsp;Joon Oh Park ,&nbsp;Kyoung-Mee Kim ,&nbsp;Deok geun Kim ,&nbsp;Jeeyun Lee ,&nbsp;Sung Hee Lim","doi":"10.1016/j.cancergen.2025.07.006","DOIUrl":"10.1016/j.cancergen.2025.07.006","url":null,"abstract":"<div><h3>Background</h3><div>Activation of the phosphatidylinositol 3-kinase (PI3K) pathway is a common oncogenic mechanism in various solid tumors and is often driven by aberrations in the <em>PIK3CA</em> gene. Recent advancements have shown effective treatment for patients with <em>PIK3CA</em>-mutated breast cancer; however, there is an unmet need for other malignancies. The aim of this study was to gain a better understanding of PIK3CA mutations and amplifications across cancer types.</div></div><div><h3>Methods</h3><div>From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3886 patients with 36 different cancer types at the Samsung Medical Center. The incidence of <em>PIK3CA</em> mutations and amplifications according to cancer type and their correlation with the tumor mutation burden (TMB), microsatellite instability (MSI), and homologous recombination deficiency (HRD) status were reviewed. Mutation sites were also identified.</div></div><div><h3>Results</h3><div>Among the 3886 patients, <em>PIK3CA</em> mutations were present in 9.2 % (358/3886) of the cohort, with colorectal cancer, 52.8 % (189/358), having the highest incidence. Patients harboring <em>PIK3CA</em> mutations demonstrated significantly higher TMB and MSI-high rates than those without (31.8 % vs. 12.5 % for TMB and 7.8 % vs. 1.6 % for MSI-high, respectively, <em>p</em> = 0.001). In contrast, <em>PIK3CA</em> amplifications were observed in 1.3 % (51/3886) of patients, primarily in gastric, bladder, and colorectal cancers, and associated with lower TMB, MSI-high, and HRD rates. PIK3CA fusions were identified in three patients. The most common mutation sites were E545K, E542K, and H1047R.</div></div><div><h3>Conclusion</h3><div>Of 3886 patients with metastatic solid tumors, 358(9.2 %) had <em>PIK3CA</em> mutations and 51(1.3 %) had PIK3CA amplifications. Next-generation sequencing analysis provided a deeper understanding of PIK3CA aberrations.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 133-143"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144656551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of pembrolizumab in MSI-high and BRCA-positive castration-resistant prostate cancer","authors":"Keita Higa ,&nbsp;Satoshi Yamamoto ,&nbsp;Koichiro Kurokawa ,&nbsp;Koki Watanabe ,&nbsp;Hiroki Bamba ,&nbsp;Sanji Kanaoka ,&nbsp;Kazuyoshi Nakamura","doi":"10.1016/j.cancergen.2025.06.002","DOIUrl":"10.1016/j.cancergen.2025.06.002","url":null,"abstract":"<div><div>This report presents a rare case of metastatic castration-resistant prostate cancer (CRPC) in an adult patient characterized by dual molecular alterations: microsatellite instability-high (MSI-H) and a BRCA2 mutation. Despite initial treatment with castration, Abiraterone, and sequential chemotherapy with docetaxel and cabazitaxel, the patient progressed to CRPC. Genetic testing revealed MSI-H and a BRCA2 mutation, prompting pembrolizumab therapy. The treatment led to a dramatic prostate-specific antigen (PSA) reduction .</div><div>This case underscores the importance of comprehensive genomic profiling for advanced prostate cancer. MSI-H tumors often respond to immune checkpoint inhibitors (ICIs) such as pembrolizumab, while BRCA2 mutations are associated with poly(ADP-ribose) polymerase inhibitors (PARPi) sensitivity. This dual alteration presents therapeutic challenges, as evidenced by pembrolizumab’s remarkable efficacy in this patient, highlighting its potential as a treatment option for MSI-H and BRCA-positive CRPC. Moreover, next-generation sequencing (NGS) played a crucial role in identifying actionable biomarkers not detected by earlier BRCA analyses, emphasizing the necessity of thorough genetic testing.</div><div>Further research is needed to optimize treatment strategies for cases with coexisting MSI-H and BRCA mutations, including exploring the synergistic effects of ICIs and PARP i. This case demonstrates the promise of pembrolizumab and advances the understanding of genetic testing’s role in tailoring therapies for complex molecular profiles in prostate cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 41-44"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute cardiac dysfunction in patients with ovarian cancer treated with Niraparib due to TFAM mutation: A case series and functional analysis","authors":"Fei Liu ,&nbsp;Wen Liu ,&nbsp;Danya Li ,&nbsp;Chunhua Tu ,&nbsp;Xiaoping Peng ,&nbsp;Yuan Wen","doi":"10.1016/j.cancergen.2025.05.006","DOIUrl":"10.1016/j.cancergen.2025.05.006","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian cancer is a leading cause of gynecological cancer mortality. Despite Niraparib's efficacy in increasing progression-free survival for recurrent ovarian cancer, its potential cardiotoxic effects are underexplored.</div></div><div><h3>Objective</h3><div>We performed a case series analysis involving two postmenopausal sisters who developed heart failure subsequent to Niraparib therapy for recurrent ovarian cancer.</div></div><div><h3>Methods</h3><div>Utilizing targeted next-generation sequencing (NGS), we identified a novel missense mutation c.98T&gt;A in Mitochondrial Transcription Factor A (<em>TFAM</em>) gene, which was subsequently confirmed by Sanger sequencing. To investigate the cardiotoxic effects of Niraparib, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC<img>CMs) carrying the identified mutation. The impact of the mutation on gene expression and protein levels was evaluated through real-time PCR and Western blot analyses.</div></div><div><h3>Results</h3><div>Two postmenopausal sisters treated with Niraparib suffered significant cardiac dysfunction. NGS identified a novel c.98T&gt;A variant in <em>TFAM</em> gene, resulting in a missense mutation. HEK293T cells transfected with mutant plasmids demonstrated normal expression of full-length <em>TFAM</em> mRNA and protein. hiPSC<img>CMs model revealed the variant alone did not induce cardiomyopathy. However, it predisposed to Niraparib-induced cardiomyopathy-like toxicity, mediated by metabolic dysregulation and increased cellular apoptosis</div></div><div><h3>Conclusion</h3><div>Our study revealed a novel <em>TFAM</em> variant which might induce potential cardiovascular toxicity of anticancer Niraparib therapies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 25-30"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of HOTAIR gene variants on the development of bladder cancer and its clinicopathological characteristics in a Caucasian population","authors":"Yakup Akkoç ,&nbsp;Hasan Sulhan ,&nbsp;Ersin Akgöllü ,&nbsp;Ali Çift","doi":"10.1016/j.cancergen.2025.07.007","DOIUrl":"10.1016/j.cancergen.2025.07.007","url":null,"abstract":"<div><h3>Background</h3><div>The age-adjusted rate of Bladder cancer (BC) in Türkiye is quite high, and genetic factors are effective in BC. Long non-coding RNAs (lncRNAs) synthesized from the <em>HOTAIR</em> gene have been shown to promote tumor progression in many cancers. rs874945 and rs4759314 polymorphisms in the <em>HOTAIR</em> gene cause changes in the expression levels of lncRNAs synthesized from this gene. The aim of this study was to explore for the first time the association of these variants with BC in a Caucasian population.</div></div><div><h3>Methods</h3><div>The present study explored the <em>HOTAIR</em> gene polymorphisms in 98 BC patients and in 150 healthy individuals using real-time polymerase chain reaction (RT-PCR).</div></div><div><h3>Results</h3><div>Carrying rs874945 G allele and GA genotype increased the BC risk in the statistic models. However, even if rs4759314 variant increased of BC risk was not significant. Similarly, although both polymorphisms increased clinicopathological features associated with poor prognosis, they were not statistically significant. Moreover, being older than 60 years and smoking are independent risk factors for BC.</div></div><div><h3>Discussion</h3><div>The current study is the first to show that patients carrying the G allele of the rs874945 polymorphism have a higher risk of BC in the Caucasian population. This work suggests that rs4759314 polymorphism should be studied in the Caucasian population with a larger sample size of BC patients.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296 ","pages":"Pages 145-149"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144662820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}