Cancer Genetics最新文献

{"title":"Integrating radiomics and gene expression by mapping on the image with improved DeepInsight for clear cell renal cell carcinoma","authors":"Daisuke Kawahara ,&nbsp;Misato Kishi ,&nbsp;Yuzuha Kadooka ,&nbsp;Kota Hirose ,&nbsp;Yuji Murakami","doi":"10.1016/j.cancergen.2025.02.004","DOIUrl":"10.1016/j.cancergen.2025.02.004","url":null,"abstract":"<div><h3>Background</h3><div>Radiomics analysis extracts high-dimensional features from medical images, which are used to predict outcomes in machine learning (ML). Recently, deep-learning methods have become applicable to image data converted from nonimage samples.</div></div><div><h3>Purpose</h3><div>This study conducted a comparative analysis of outcome-prediction performance using radiomics with a conventional ML approach and deep-learning (DL) approach utilising DeepInsight. Furthermore, we enhance the DeepInsight model by integrating radiomics features with gene expression data. This integration aims to improve predictive power and provide a more comprehensive understanding of ccRCC, ultimately contributing to more personalized and effective treatment strategies.</div></div><div><h3>Methods</h3><div>A total of 142 patients with clear cell renal cell carcinoma who underwent surgery were divided into training and test datasets. Radiomics features were extracted in the entire tumour region from CT images. The two-year disease-free survival was predicted using ML and DL. ML was used for selective features after LASSO regression. ML algorithms were employed for classification, including the support vector machine, k-nearest neighbour, and neural network classifiers. For DL, radiomics features and gene-expression data were converted into image data with DeepInsight, and classification tasks were performed with DL techniques such as AlexNet, SqueezeNet, and InceptionNet.</div></div><div><h3>Results</h3><div>For ML, 17 prognosis-related radiomic features were selected from the LASSO regression. The ML accuracy was 76.5 %, 71.4 %, and 78.1 % for the support vector machine, k-nearest neighbour, and neural network models, respectively. For DL, the accuracies were 76.7 %, 83.1 %, and 85.4 % for AlexNet, SqueezeNet, and InceptionNet, respectively. Furthermore, the integrated DeepInsight models exhibited the highest accuracy of 90.9 %.</div></div><div><h3>Conclusion</h3><div>The proposed DL approach utilising DeepInsight demonstrated a significant improvement in outcome-prediction performance compared with the conventional ML approach. Furthermore, the integration of DL with radiomics features and gene-expression data effectively captures the relationship between biological information and image data, rendering it a promising tool for enhancing outcome-prediction capabilities.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 100-105"},"PeriodicalIF":1.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454964","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":"Novel Co-frameshift mutations in N- and C-terminal regions of CEBPA in acute myeloid leukemia: A case report","authors":"Mohammad Mousaei Ghasroldasht ,&nbsp;Shiva Vaheb Hosseinabadi ,&nbsp;Razieh Ebrahimi Askari ,&nbsp;Reihaneh Lotfalipour","doi":"10.1016/j.cancergen.2025.02.003","DOIUrl":"10.1016/j.cancergen.2025.02.003","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is a hematologic malignancy marked by abnormal myeloid cell proliferation or differentiation arrest in the bone marrow. AML prognosis is influenced by genetic mutations, including in NPM1, FLT3-ITD, cKIT, and CEBPA genes. CEBPA, located on chromosome 19q13.11, is critical for myeloid differentiation in the hematopoietic system, and mutations in this gene occur in about 10–15 % of de novo AML cases. These mutations often appear as frameshift alterations in the N-terminal or in-frame insertions/deletions in the C-terminal basic leucine zipper (bZIP) domain. We report a unique CEBPA mutation profile in a 19-year-old male with AML, normal karyotype, and no mutations in FLT3-ITD, NPM1, or cKIT. The patient exhibited a frameshift mutation in the N-terminal region and a novel in-frame duplication in the C-terminal regions of CEBPA, which has not been previously reported in AML. This case emphasizes the importance of genetic profiling in identifying clinically relevant mutation patterns and highlights the potential of genetic insights to inform personalized treatment. It also underscores the need for further studies on the functional implications of unique CEBPA mutations in AML pathogenesis.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 73-76"},"PeriodicalIF":1.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420236","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":"Anaplastic meningioma in a 6-year-old with somatic YAP1::MAML2 fusion and multiple endocrine neoplasia type 4 (MEN4) syndrome","authors":"Lauren R. Desrosiers-Battu ,&nbsp;John H. Lee ,&nbsp;Izabela Tarasiewicz ,&nbsp;Andrea R. Gilbert ,&nbsp;Eva M Galvan ,&nbsp;Achint K. Singh ,&nbsp;Angshumoy Roy ,&nbsp;George Miles ,&nbsp;Jacquelyn Reuther ,&nbsp;Donna M. Muzny ,&nbsp;Bo Yuan ,&nbsp;Shashikant Kulkarni ,&nbsp;Christine Eng ,&nbsp;Sarah Scollon ,&nbsp;Shawn Gessay ,&nbsp;Amy L. McGuire ,&nbsp;D. Williams Parsons ,&nbsp;Gail E. Tomlinson ,&nbsp;Sharon E. Plon ,&nbsp;Shafqat Shah","doi":"10.1016/j.cancergen.2025.01.009","DOIUrl":"10.1016/j.cancergen.2025.01.009","url":null,"abstract":"<div><div>Meningiomas are the most common primary brain tumors in adults but much less frequent in children. Many subtypes exist, including anaplastic (malignant) meningioma, which accounts for less than 20% of pediatric tumors. Meningiomas can arise in association with cancer predisposition syndromes due to germline variants in genes such as <em>NF2, MEN1</em> and <em>SMARCE1</em>. This report describes a 6-year-old boy diagnosed with anaplastic meningioma who was treated with surgery and focal radiation therapy. The family consented to participate in the Texas KidsCanSeq clinical genomics study. Analysis of germline and tumor samples detected a single germline finding of a <em>CDKN1B</em> pathogenic frameshift variant associated with Multiple Endocrine Neoplasia Type 4 (MEN4) without somatic loss of the other allele. Tumor analysis revealed a <em>YAP1</em>::<em>MAML2</em> fusion, which has been previously reported in pediatric meningiomas not associated with NF2. <em>YAP1</em>::<em>MAML2</em> fusion is a known driver for development of meningioma, but the role of the germline <em>CDKN1B</em> variant in the absence of a tumor second hit is unclear. This case highlights the importance of performing combined tumor and germline molecular genetic analysis of rare tumors to help clarify the risk of development of cancer in patients with rare cancer predisposition syndromes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 106-110"},"PeriodicalIF":1.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465373","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":"De novo RUNX1-driven acute myeloid leukemia requiring integrative genetics","authors":"Celeste C. Eno ,&nbsp;Jeremy Lorber ,&nbsp;Eric Vail ,&nbsp;Rhona Schreck","doi":"10.1016/j.cancergen.2025.02.002","DOIUrl":"10.1016/j.cancergen.2025.02.002","url":null,"abstract":"<div><div>Copy number variants are common in myeloid malignancies and may hold diagnostic, prognostic or therapeutic significance. We present a case of acute myeloid leukemia driven by a <em>RUNX1</em> deletion with no prior history of a myeloid neoplasm. Discovery of the underlying genetic lesion required multiple testing platforms highlighting the strengths and weaknesses of each test type. Additionally, this case adds to the literature of <em>RUNX1</em> deletion AML, the adverse prognosis that these cases share and the potential consideration of <em>RUNX1</em> alterations (both deletions and mutations) as a specific AML entity.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 69-72"},"PeriodicalIF":1.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372046","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 mechanism of E3 ubiquitin ligase HERC1 regulating ferroptosis in lung adenocarcinoma cells","authors":"Fei Ye ,&nbsp;Yi Xu ,&nbsp;Xujuan Zhu ,&nbsp;Qifeng Ding ,&nbsp;Yifei Wang ,&nbsp;Songhua Lu ,&nbsp;Yongbing Chen","doi":"10.1016/j.cancergen.2025.02.001","DOIUrl":"10.1016/j.cancergen.2025.02.001","url":null,"abstract":"<div><h3>Objective</h3><div>Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer. Herein, we probed into the role of E3 ubiquitin protein ligase family member 1 (HERC1) in promoting ferroptosis and inhibiting LUAD cell proliferation by regulating RAF proto-oncogene serine/threonine-protein kinase (C-RAF).</div></div><div><h3>Methods</h3><div>In cultured human normal lung epithelial cells and non-small cell lung adenocarcinoma cell lines, HERC1 expression was determined by RT-qPCR and Western blot tests. PC-9 and Calu-3 cells were transfected with oe-HERC1, oe-C-RAF or their negative controls. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe²⁺ levels were assessed by biochemical assays. Cell viability, death, and proliferation were evaluated by CCK-8, LDH and colony formation assays, followed by assessments of HERC1-C-RAF interaction, C-RAF ubiquitin level, and C-RAF protein stability.</div></div><div><h3>Results</h3><div>HERC1 was poorly expressed in LUAD cells. HERC1 promoted LUAD cell ferroptosis and repressed their proliferation and migration, corresponding to reduced levels of system xc-, GPX4, and GSH, as well as elevated levels of ROS, MDA, Fe²⁺, and ACSL4. LUAD cells overexpressing HERC1 displayed decreased C-RAF protein level, HERC1-C-RAF interaction, elevated C-RAF ubiquitin level, and accelerated C-RAF protein degradation, indicating that HERC1 facilitated C-RAF ubiquitin degradation and attenuated C-RAF protein stability <em>via</em> interaction with C-RAF. C-RAF overexpression partially abrogated the regulatory impact of HERC1 on LUAD cell ferroptosis and proliferation.</div></div><div><h3>Conclusion</h3><div>HERC1 expedites C-RAF ubiquitin degradation by interacting with C-RAF, which consequently promotes ferroptosis, thereby inhibiting LUAD cell proliferation.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 92-99"},"PeriodicalIF":1.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454963","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":"Clinical and genetic characteristics in two cases of Birt-Hogg-Dubé syndrome associated with papillary renal cell carcinoma and rare Folliculin (FLCN) variants","authors":"Mark G. Evans ,&nbsp;Logan W. Thomas ,&nbsp;Manando Nakasaki ,&nbsp;Ahmad Charifa ,&nbsp;Anthony Sisk ,&nbsp;Sandy Liu ,&nbsp;Lawrence F. Kuklinski ,&nbsp;Brian Shuch ,&nbsp;Fabiola Quintero-Rivera","doi":"10.1016/j.cancergen.2025.01.007","DOIUrl":"10.1016/j.cancergen.2025.01.007","url":null,"abstract":"<div><div>Birt-Hogg-Dubé syndrome (BHDS) is characterized by autosomal dominant alterations in the <em>Folliculin (FLCN)</em> gene, resulting in cutaneous, pulmonary, and renal abnormalities. In particular, affected individuals are susceptible to the development of renal cell carcinoma (RCC), which most frequently present as chromophobe tumors or hybrid cancers with features of oncocytoma and chromophobe RCC. Type 1 and type 2 papillary neoplasms have rarely been described in the setting of BHDS, and we present two additional cases. Utilizing next-generation sequencing, the patients were found to harbor germline <em>FLCN</em> variants that are not well-documented in the medical literature. While RCCs associated with BHDS are thought to portend a better prognosis compared to their non-syndromic counterparts, the patients described here experienced variable clinical outcomes—one developed locally aggressive disease, distant metastases, and quickly succumbed to his disease.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 65-68"},"PeriodicalIF":1.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081813","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":"False positive NUP98 fluorescence in situ hybridization rearrangements in B-acute lymphoblastic leukemia","authors":"Marie-France Gagnon ,&nbsp;Sahil S. Tonk ,&nbsp;Benjamin Carcamo ,&nbsp;Daniel Bustamante ,&nbsp;Mariam Stein ,&nbsp;Sarah H. Johnson ,&nbsp;George Vasmatzis ,&nbsp;Cinthya J. Zepeda-Mendoza ,&nbsp;Patricia T. Greipp ,&nbsp;Xinjie Xu ,&nbsp;Rhett P. Ketterling ,&nbsp;Jess F. Peterson ,&nbsp;Wenjing Wang ,&nbsp;Yajuan J. Liu ,&nbsp;Vijay Tonk ,&nbsp;Karen Tsuchiya ,&nbsp;Santosh Chavali ,&nbsp;Linda B. Baughn","doi":"10.1016/j.cancergen.2025.01.006","DOIUrl":"10.1016/j.cancergen.2025.01.006","url":null,"abstract":"<div><div>Gene fusions involving <em>NUP98</em> have been reported in several hematologic malignancies yet have been very rarely reported in B-acute lymphoblastic leukemia (B-ALL). Two cases of B-ALL for which chromosome banding analysis (CBA) and fluorescence in situ hybridization (FISH) suggested apparent <em>NUP98</em> rearrangements were further investigated with next-generation sequencing-based methodologies to verify the findings obtained with traditional cytogenetic methodologies. In the first case, CBA revealed a hyperdiploid karyotype with multiple structural abnormalities including additional material of unknown origin at 11p15; subsequent break-apart probe (BAP) FISH for <em>NUP98</em> demonstrated 2 intact fusion signals and a single separate 5′<em>NUP98</em> signal. However, whole-genome sequencing found no evidence of a <em>NUP98</em> gene fusion. The results obtained with conventional cytogenetic methodologies were in fact attributable to structural variants (SV) with breakpoints not within <em>NUP98</em> but within the 5′<em>NUP98</em> BAP probe-binding sequence. In the second case, CBA revealed several structural and numeric abnormalities including a complex translocation between chromosomes 11 (at 11p15.4) and 19 (at 19p13.3) and an insertion of unknown material at 11p15.4. BAP FISH demonstrated a typical FISH signal pattern consistent with an apparent <em>NUP98</em> rearrangement. However, no evidence of a <em>NUP98</em> fusion was found on RNA sequencing. In conclusion, the two cases thus presented with clinical false positive <em>NUP98</em> rearrangements by FISH. In the clinical laboratory, SVs in the vicinity of genes involved in recurrent rearrangements in hematologic malignancies may result in misleading results with conventional chromosome methodologies. This may preclude an accurate definition of the genetic attributes of malignancies with ensuing impacts on risk stratification and management. Higher-resolution testing methodologies such as whole-genome sequencing and RNA sequencing may be helpful in resolving unexpected results with conventional chromosome methodologies and enhancing the accuracy of genetic characterization of hematological malignancies in the clinical laboratory.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 57-64"},"PeriodicalIF":1.4,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatoblastoma in a patient with neurofibromatosis type 1: A case report","authors":"A. Praga ,&nbsp;T.Z. Hirsch ,&nbsp;D. Vidaud ,&nbsp;V. Laithier ,&nbsp;E. Puzenat ,&nbsp;J. Zucman-Rossi ,&nbsp;C. Mussini ,&nbsp;P. Kuentz ,&nbsp;J. Piard","doi":"10.1016/j.cancergen.2025.01.005","DOIUrl":"10.1016/j.cancergen.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>Neurofibromatosis type 1 (NF1) is one of the most common genodermatoses. It can affect every organ and is associated with an increased risk of benign and malignant tumors. Most common tumoral locations involve nervous system and soft tissues but a large variety of tumors have been described. So far, hepatoblastoma in a patient with NF1 has been reported twice in the literature.</div></div><div><h3>Case presentation</h3><div>A liver mass was discovered in a 11 year-old girl with NF1 leading to a diagnosis of epithelial hepatoblastoma with pulmonary metastasis. Targeted analysis on blood revealed a germline <em>NF1</em> missense variant. Exome sequencing, RNA-seq and methylation analyses performed on tumoral and metastatic samples confirmed the germline <em>NF1</em> variant and showed classical driver variants for hepatoblastoma.</div></div><div><h3>Conclusions</h3><div>We present here the third case of hepatoblastoma in a patient with NF1 and discuss the possible link between this rare tumor and this neurocutaneous genetic condition.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 35-37"},"PeriodicalIF":1.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel POT1-TPD presentation: A germline pathogenic POT1 variant discovered in a patient with newly diagnosed posterior fossa ependymoma","authors":"Stephen Gilene ,&nbsp;Sara Knapke ,&nbsp;Daniel Leino ,&nbsp;Somak Roy ,&nbsp;Scott Raskin","doi":"10.1016/j.cancergen.2025.01.004","DOIUrl":"10.1016/j.cancergen.2025.01.004","url":null,"abstract":"<div><h3>Introduction</h3><div><em>POT1</em> tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently reported malignancies [<span><span>1</span></span>]. Protection of telomeres protein 1 (<em>POT1</em>) is part of the shelterin protein complex to maintain/protect telomeres [<span><span>2</span></span>]. Proposed mechanisms for oncogenesis with <em>POT1</em> loss of function include telomere elongation and DNA damage response causing genomic instability [<span><span>3</span></span>]. Ependymomas are a heterogeneous group representing one-third of pediatric brain tumors and are locally aggressive with frequent recurrence [<span><span>4</span></span>].</div></div><div><h3>Case presentation</h3><div>A healthy 3-year-old male presented with worsening vertigo, headaches, and emesis. Radiographic studies demonstrated a midline posterior fossa mass in the fourth ventricle. Following a gross total resection, pathology demonstrated a posterior fossa ependymoma, group A. Next generation sequencing (NGS) using our institution's clinically validated panel, “CinCSeq,” identified a <em>POT1</em> splice site variant (c.1164–1G&gt;<em>A</em>; variant allele fraction 46 %). Paired germline testing via the Molecular Characterization Initiative confirmed this variant as heterozygous in the patient. Genetic testing confirmed the <em>POT1</em> pathogenic variant in his mother, who has a history of multiple nevi. The patient completed treatment with focal proton radiotherapy with no evidence of disease recurrence to date.</div></div><div><h3>Discussion</h3><div>To our knowledge, this represents the first documented pediatric ependymoma patient with a familial, germline <em>POT1</em> pathogenic variant. Somatic <em>POT1</em> mutational frequency, as determined by NGS in over 60,000 solid tumors, is 2.94 %. Among this cohort, 48 cases were ependymomas with one non-benign <em>POT1</em> mutation [<span><span>5</span></span>]. Alterations of telomere maintenance have been reported in intracranial ependymomas previously through increased human telomerase reverse transcriptase (hTERT) expression [<span><span>6</span></span>,<span><span>7</span></span>]. This case sheds light on a potential new predisposition for ependymoma development and the expanding phenotype of POT1-TPD. We recognize the <em>POT1</em> pathogenic variant may have been discovered incidentally in this case. Further research is needed to advance our understanding of the association between POT1 genetic alterations and ependymomas.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 38-43"},"PeriodicalIF":1.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of transcription factor TWIST1 in bladder cancer progression","authors":"Meryem EL Azzouzi ,&nbsp;Boutaina Addoum ,&nbsp;Hajar El Ahanidi ,&nbsp;Ilias Hassan ,&nbsp;Mohammed Tetou ,&nbsp;Ahmed Ameur ,&nbsp;Abderrahmane Al Bouzidi ,&nbsp;Mohamed Oukabli ,&nbsp;Laila Benbacer ,&nbsp;Mohammed Attaleb ,&nbsp;Mohammed El Mzibri ,&nbsp;Imane Chaoui","doi":"10.1016/j.cancergen.2025.01.003","DOIUrl":"10.1016/j.cancergen.2025.01.003","url":null,"abstract":"<div><div>The transcription factor <em>TWIST1</em> is a major regulator of Epithelial-Mesenchymal Transition, enhancing cancer cell mobility and invasive potential. Overexpression of <em>TWIST1</em> is associated with tumor progression and poor prognosis. In our study, we explored the role of TWIST1 as both a prognostic biomarker and a therapeutic target in bladder cancer (BC), as well as the relationship between its promoter methylation and mRNA expression in bladder cancer patients. In cohort of 66 bladder cancer patients, we explored <em>TWIST1</em> expression levels in tumor samples through RT-qPCR analysis;</div><div>Our findings revealed a significant correlation between high <em>TWIST1</em> expression levels and advanced bladder tumor stages, grades, and progression; suggesting its association with aggressive BC phenotypes. Importantly, patients with low <em>TWIST1</em> expression exhibited significantly prolonged disease-free survival (DFS), indicating its potential as a prognostic marker for stratification and as a therapeutic target in advanced BC. In contrast, there was no direct correlation between <em>TWIST1</em> promoter methylation status and <em>TWIST1</em> expression levels in BC tumors.</div><div>In summary, <em>TWIST1</em> expression could play an important role as a molecular marker for BC patients’ prognosis and overall survival prediction. Moreover, our results suggest that <em>TWIST1</em> promoter methylation doesn't affect the gene expression in BC. Furthermore, understanding the molecular mechanisms driving <em>TWIST1</em> dysregulation may uncover novel therapeutic targets to improve the management of BC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"292 ","pages":"Pages 44-48"},"PeriodicalIF":1.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053948","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}