Cancer Genetics最新文献

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Molecular mechanisms underlying the oncogenic and tumor-suppressive roles of ZHX2 in cancers 肿瘤中ZHX2的致癌和肿瘤抑制作用的分子机制
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-20 DOI: 10.1016/j.cancergen.2025.09.010
Yifan Wei , Haiyang Guo , Jingjie Zhou , Da Shi, Liqiang Hao
{"title":"Molecular mechanisms underlying the oncogenic and tumor-suppressive roles of ZHX2 in cancers","authors":"Yifan Wei ,&nbsp;Haiyang Guo ,&nbsp;Jingjie Zhou ,&nbsp;Da Shi,&nbsp;Liqiang Hao","doi":"10.1016/j.cancergen.2025.09.010","DOIUrl":"10.1016/j.cancergen.2025.09.010","url":null,"abstract":"<div><div>The transcription factor ZHX2 exerts paradoxical roles in cancer, acting as either an oncogene or tumor suppressor in a context-dependent manner. This duality stems from ZHX2’s regulation of key processes including cell cycle, apoptosis, EMT, stemness, and metabolism. Consequently, ZHX2 may impacts tumor cell growth, migration, and immune evasion, positioning it as a promising therapeutic target. This short communication synthesizes current understanding of ZHX2’s molecular structure, transcriptional regulation, and its critical modulation of oncogenic and tumor-suppressive pathways across various cancers. We highlight its potential utility as a prognostic biomarker and its implications for precision medicine, chemotherapy, targeted therapy, and immunotherapy. However, translating ZHX2-targeting strategies faces significant hurdles, particularly concerning tissue-specific restoration and integration with existing treatments. Future research should prioritize overcoming these barriers and exploring ZHX2’s epigenetic regulatory potential.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 128-132"},"PeriodicalIF":2.1,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118517","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}
引用次数: 0
Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients IDH1/2突变对成人急性髓性白血病患者预后的差异影响
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-18 DOI: 10.1016/j.cancergen.2025.09.008
Wanfang Yang , Jing Xu , Shuhua Cao , Ning Wang , Zhuanghui Hao , Qing Wang , Yanhong Tan , Xiuhua Chen , Zhifang Xu , Yaofang Zhang , Jianmei Chang , Xiaojuan Wang , Fanggang Ren , Hongwei Wang
{"title":"Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients","authors":"Wanfang Yang ,&nbsp;Jing Xu ,&nbsp;Shuhua Cao ,&nbsp;Ning Wang ,&nbsp;Zhuanghui Hao ,&nbsp;Qing Wang ,&nbsp;Yanhong Tan ,&nbsp;Xiuhua Chen ,&nbsp;Zhifang Xu ,&nbsp;Yaofang Zhang ,&nbsp;Jianmei Chang ,&nbsp;Xiaojuan Wang ,&nbsp;Fanggang Ren ,&nbsp;Hongwei Wang","doi":"10.1016/j.cancergen.2025.09.008","DOIUrl":"10.1016/j.cancergen.2025.09.008","url":null,"abstract":"<div><div>Mutations in Isocitrate Dehydrogenase-1 (IDH1) and IDH2 lead to abnormal histone hypermethylation and DNA modifications, disrupting cell differentiation, yet the clinical and prognostic significance of these mutations in primary acute myeloid leukemia (AML) remains debated. This study retrospectively analyzed 181 newly diagnosed AML patients, categorizing them into IDH1mut, IDH2mut, and IDHwt groups to compare clinical features, mutational profiles, and outcomes. IDH1 and IDH2 mutations were detected in 7.7 % (14/181) and 11.6 % (21/181) of cases, respectively. Patients with IDH mutations were older, had higher platelet counts, elevated WT1 mRNA expression, and lower white blood cell counts compared to IDHwt patients. Notably, IDH1mut patients showed no significant OS difference (<em>P</em> = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008–3.792, <em>P</em> = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (<em>P</em> = .013 and <em>P</em> = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (<em>P</em> &lt; .05).</div><div>These findings suggest that early detection of IDH1/2 mutations and associated clinical features at AML diagnosis could provide a rationale for targeted therapy with IDH inhibitors, potentially improving patient outcomes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 133-140"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118431","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}
引用次数: 0
Comparison of somatic variant oncogenicity classification using ClinGen/CGC/VICC guidelines and QIAGEN Clinical Insight Interpret decision support software 使用ClinGen/CGC/VICC指南和QIAGEN临床洞察解释决策支持软件进行体细胞变异致癌性分类的比较
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-18 DOI: 10.1016/j.cancergen.2025.09.009
Aarthi Goverdhan , Lisa Mullineaux , Amber Pryzbylski , Claire Teigen , Kevin C. Halling , Sheryl K. Elkin , Beth A. Pitel
{"title":"Comparison of somatic variant oncogenicity classification using ClinGen/CGC/VICC guidelines and QIAGEN Clinical Insight Interpret decision support software","authors":"Aarthi Goverdhan ,&nbsp;Lisa Mullineaux ,&nbsp;Amber Pryzbylski ,&nbsp;Claire Teigen ,&nbsp;Kevin C. Halling ,&nbsp;Sheryl K. Elkin ,&nbsp;Beth A. Pitel","doi":"10.1016/j.cancergen.2025.09.009","DOIUrl":"10.1016/j.cancergen.2025.09.009","url":null,"abstract":"<div><div>Accurate clinical interpretation of somatic cancer variants is critical for diagnosis and guidance of precision oncology treatment. As the depth and breadth of genomic sequencing increased, laboratories developed independent standards for the classification of somatic variants. In response, a set of standards for classification were published by a collaboration among Clinical Genome Resource (ClinGen), Cancer Genomics Consortium (CGC) and Variant Interpretation for Cancer Consortium (VICC). This study evaluated these standards and compared the resulting classifications to the classifications generated by a clinical decision support software system, QIAGEN Clinical Insight (QCI) Interpret One, a system using a version of the 2015 consensus guidelines by the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) customized for somatic assessment. The published variant set for validation was utilized and expanded by conducting a retrospective analysis using real-world cancer variants drawn from oncology cases tested at Mayo Clinic. For “oncogenic” and “likely oncogenic” variants in the combined datasets, automated classifications by the QCI system were 97.2% concordant with those assessed using the ClinGen/CGC/VICC system. The ClinGen/CGC/VICC standards led to more conservative variant classifications, with a larger proportion of variants assigned to the “variant of unknown significance” and “likely benign” designations. This study demonstrates that the ClinGen/CGC/VICC guidelines and clinical decision support tools can be effectively used together to facilitate somatic variant classification and interpretation.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 151-158"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158113","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}
引用次数: 0
The multidimensional role of laminin γ2 (LAMC2) on cancer progression 层粘连蛋白γ - 2 (LAMC2)在癌症进展中的多维作用
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-16 DOI: 10.1016/j.cancergen.2025.09.007
Xiaojuan Zhang , Juan Xie , Tao Fu , Zhen Gao , Hengrui Liu , Zhenshan Yang
{"title":"The multidimensional role of laminin γ2 (LAMC2) on cancer progression","authors":"Xiaojuan Zhang ,&nbsp;Juan Xie ,&nbsp;Tao Fu ,&nbsp;Zhen Gao ,&nbsp;Hengrui Liu ,&nbsp;Zhenshan Yang","doi":"10.1016/j.cancergen.2025.09.007","DOIUrl":"10.1016/j.cancergen.2025.09.007","url":null,"abstract":"<div><div>Laminin, a critical component of the basement membrane, plays an indispensable role in numerous biological processes. Among its subunits, laminin γ2 (LAMC2) emerges as a key player in the progression of cancer. This review delves into the current understanding of LAMC2′s role, highlighting its significant contribution to cancer development through promoting cell proliferation, invasion, and vasculogenic mimicry, as well as inhibiting apoptosis. Notably, LAMC2 expression is markedly increased in cancerous tissues compared to normal counterparts, with higher levels of LAMC2 correlating with poorer survival rates. This correlation underscores LAMC2′s potential as a diagnostic and prognostic marker across various cancers. Furthermore, the increasing importance of LAMC2 as a viable target for cancer therapy is explored. This review aims to provide a thorough overview of LAMC2′s involvement in cancer progression, prognostic implications, potential therapeutic target, and involved signaling pathway, and to outline future research directions in this promising field.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 122-127"},"PeriodicalIF":2.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145109630","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}
引用次数: 0
Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype 半凝集素-9通过使巨噬细胞向M2表型极化促进结肠癌的发展
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-10 DOI: 10.1016/j.cancergen.2025.09.006
Jun Zhang , Yang Xu , Xiao Han , Yan Gao , Zhanbo Wei , Xu Sun
{"title":"Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype","authors":"Jun Zhang ,&nbsp;Yang Xu ,&nbsp;Xiao Han ,&nbsp;Yan Gao ,&nbsp;Zhanbo Wei ,&nbsp;Xu Sun","doi":"10.1016/j.cancergen.2025.09.006","DOIUrl":"10.1016/j.cancergen.2025.09.006","url":null,"abstract":"<div><div>Galectin-9 plays multiple roles in various tumors and exerts immune regulation within the tumor microenvironment. It is closely associated with tumor prognosis. This study aimed to analyze the expression of galectin-9 in the colon tumor microenvironment. The results indicated that galectin-9 expression is higher in the colon tumor microenvironment compared to adjacent normal tissues. Furthermore, high expression of galectin-9 was related to M2-type macrophages, which promote tumor development by increasing tumor cell viability, migration, and invasion. Notably, high expression of galectin-9 in colon tumor microenvironment contributed to the polarization of M2 cells, marked by high expression of arginase-1, CD163, and IL-10 and low expression of iNOS. When M0 macrophages were treated with galectin-9 and co-cultured with colon cancer cell lines, it resulted in increased cancer cell growth, migration, and invasion by promoting the differentiation of THP-1 monocytes into the M2 macrophages. The specific mechanism by which galectin-9 promotes M2 polarization involves its binding to Tim-3, recruiting PI3K-p85 to the cytoplasmic domain of Tim-3. This interaction further affects the PI3K/Akt signal pathway, leading to M2 polarization.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 141-150"},"PeriodicalIF":2.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158112","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}
引用次数: 0
Development and multi-cohort validation of a prognostic risk score model for oral squamous cell carcinoma based on a three-gene signature 基于三基因标记的口腔鳞状细胞癌预后风险评分模型的开发和多队列验证
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-05 DOI: 10.1016/j.cancergen.2025.09.005
Junxu Chen , Dongwook Kim , Jae Young Kim , Hyung Jun Kim
{"title":"Development and multi-cohort validation of a prognostic risk score model for oral squamous cell carcinoma based on a three-gene signature","authors":"Junxu Chen ,&nbsp;Dongwook Kim ,&nbsp;Jae Young Kim ,&nbsp;Hyung Jun Kim","doi":"10.1016/j.cancergen.2025.09.005","DOIUrl":"10.1016/j.cancergen.2025.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care.</div></div><div><h3>Methods</h3><div>Transcriptomic and clinical data from TCGA and multiple GEO cohorts were integrated. Candidate genes identified by differential expression analysis, WGCNA, and PPI were refined using LASSO and Random Forest, then entered a multivariable Cox model to derive a three-gene risk score. Performance was assessed with Kaplan–Meier curves, time-dependent ROC, and calibration, and validated across internal, external, and combined datasets. Expression was examined by RT-qPCR and Western blot in OSCC and normal oral cell lines. Immune infiltration and pathway enrichment analyses were conducted to contextualize biology.</div></div><div><h3>Results</h3><div>The three-gene signature (<em>CXCL12, PLAU, PXDN</em>) separated risk groups in the training cohort with 1/3/5-year AUCs of 0.767/0.625/0.714. In three independent external cohorts, high-risk patients consistently had worse overall survival (log-rank <em>p</em> = 0.0092, ≤0.0001, ≤0.0001), with time-AUC ranges of 0.581–0.747 (1-year), 0.555–0.795 (3-year), and 0.603–0.812 (5-year). In TCGA, the score remained prognostic across sex, age, smoking, drinking, and stage III/IV subgroups (all <em>p</em> ≤ 0.05), with a consistent trend in stage I/II (<em>p</em> = 0.09). A nomogram integrating clinical variables with the risk score achieved a C-index of 0.63 with good 1–5-year calibration and outperformed TNM staging alone (C-index 0.63 vs 0.58; 95 % CI 0.58–0.70 vs 0.54–0.61). RT-qPCR/Western blot confirmed consistent differential expression of all three biomarkers. Immune-infiltration and pathway analyses revealed distinct microenvironmental and molecular features across risk strata.</div></div><div><h3>Conclusion</h3><div>We present a robust, externally validated three-gene prognostic model for OSCC, supported by experimental evidence and superior to TNM staging for discrimination, offering a practical nomogram for individualized risk estimation from 1 to 5 years.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 88-98"},"PeriodicalIF":2.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048476","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}
引用次数: 0
A pilot study of evaluation of a deep-learning-based homologous recombination deficiency assay in korean patients with ovarian high-grade serous carcinoma: Diagnostic performance and clinical implications 一项评估基于深度学习的同源重组缺陷测定在韩国卵巢高级别浆液性癌患者中的初步研究:诊断性能和临床意义
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-04 DOI: 10.1016/j.cancergen.2025.09.003
Gui Young Kwon , Sanghoo Lee , Jeonghoon Hong , Yiseul Kim , Hee-Ji Choi , Jihye Yun , Jinhee Park , Jiyoon Jung , Joonsung Yoon , SaeYun Baik , Mi-Kyeong Lee , Kyoung-Ryul Lee , Jeong Won Kim
{"title":"A pilot study of evaluation of a deep-learning-based homologous recombination deficiency assay in korean patients with ovarian high-grade serous carcinoma: Diagnostic performance and clinical implications","authors":"Gui Young Kwon ,&nbsp;Sanghoo Lee ,&nbsp;Jeonghoon Hong ,&nbsp;Yiseul Kim ,&nbsp;Hee-Ji Choi ,&nbsp;Jihye Yun ,&nbsp;Jinhee Park ,&nbsp;Jiyoon Jung ,&nbsp;Joonsung Yoon ,&nbsp;SaeYun Baik ,&nbsp;Mi-Kyeong Lee ,&nbsp;Kyoung-Ryul Lee ,&nbsp;Jeong Won Kim","doi":"10.1016/j.cancergen.2025.09.003","DOIUrl":"10.1016/j.cancergen.2025.09.003","url":null,"abstract":"<div><h3>Background</h3><div>Homologous recombination deficiency (HRD)-related genetic mutations in ovarian high-grade serous carcinoma (HGSC) are known to be ethnic specific. Here, we assessed the diagnostic performance of HRD and its clinical implication in Korean HGSC patients using the SOPHiA DDM HRD Solution.</div></div><div><h3>Methods</h3><div>Sixty-three ovarian cancer (OC) patients were enrolled, including 53 with HGSC and 10 with other subtypes. HRD status was determined by 28 homologous recombination repair (HRR) genetic sequencing and genomic scarring (GS) measurement. The GS was measured through low-pass whole-genome sequencing and quantified using the genomic integrity index (GII).</div></div><div><h3>Results</h3><div>HRD status was analyzed in 53 out of 63 OC patients (84.1 %). Among the 53 with HGSC, HRD results were available for 83.0 % (<em>n</em> = 44). Of these HGSC patients, 72.7 % (<em>n</em> = 32) were HRD-positive, including 15 with <em>BRCA1/2</em> mutations (34.1 %) and 27 with GI-positive (61.4 %). In HGSC, HRD-positive status was associated with solid, pseudoendometrioid or transitional (SET) pattern (<em>P</em> = 0.015). Patients with positive HRD and high GII (&gt;4.2) exhibited improved disease-free survival (DFS) and overall survival (OS) compared to those with negative HRD (<em>P</em> = 0.003 and 0.024, respectively) and low GII (<em>P</em> &lt; 0.001 and <em>P</em> = 0.006, respectively). Multivariate analysis revealed a high GII as a better prognostic indicator for DFS and OS (<em>P</em> = 0.003 and 0.032, respectively).</div></div><div><h3>Conclusion</h3><div>The HRD assay offers high diagnostic performance of HRD in Korean OC patients. Furthermore, the prognostic value of high GII and HRD, as well as an association with SET pattern and HRD was evident in HGSC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 69-77"},"PeriodicalIF":2.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018569","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}
引用次数: 0
Hi-C analysis of amplification of MYC, PVT1, and CCDC26 on marker chromosomes in the NB-4 cell line NB-4细胞系标记染色体上MYC、PVT1和CCDC26基因扩增的Hi-C分析
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-03 DOI: 10.1016/j.cancergen.2025.09.004
Tetsuko Kobayashi , Satsuki Matsushima , Hiroaki Ohnishi
{"title":"Hi-C analysis of amplification of MYC, PVT1, and CCDC26 on marker chromosomes in the NB-4 cell line","authors":"Tetsuko Kobayashi ,&nbsp;Satsuki Matsushima ,&nbsp;Hiroaki Ohnishi","doi":"10.1016/j.cancergen.2025.09.004","DOIUrl":"10.1016/j.cancergen.2025.09.004","url":null,"abstract":"<div><div><em>MYC</em> proto-oncogene may be amplified ectopically in acute myeloid leukemia (AML) as extrachromosomal DNA (ecDNA) such as double minutes (dmins). However, the mechanism and location of <em>MYC</em> amplification have not been fully elucidated. To characterize the location of <em>MYC</em> and its surrounding structure in NB-4 cells, we conducted this study using <em>in situ</em> high-throughput chromosomal conformation capture (<em>in situ</em> Hi-C). Hi-C analysis was performed in NB-4 cell line. Whole genome sequencing (WGS) and fluorescence <em>in situ</em> hybridization (FISH) were used for confirmation. Hi-C revealed an inversion involving <em>PVT1</em> and <em>CCDC26</em> and amplified segments involving <em>MYC, PVT1</em>, and <em>CCDC26</em> on 8q24.21 region. <em>MYC, PVT1</em>, and <em>CCDC26</em> were found not only on chromosome 8, but also somewhere intranuclear, other than on chromosome 8. Karyotyping revealed only two normal chromosomes 8, and the others were missing or abnormal. FISH revealed the presence of <em>MYC, PVT1</em>, and <em>CCDC26</em> on the two normal chromosomes 8 and multiple marker chromosomes. Our results suggest that the numerical and structural abnormalities of chromosome 8 precede <em>MYC</em> amplification and moving. <em>MYC</em> may have properties that move not only to dmins, but also to other chromosomes such as marker chromosomes for unknown but certain reasons. <em>MYC</em> ectopic amplification is not only a phenomenon in solid tumors, but also a recurrent phenomenon in AML. Furthermore, in a broader sense, ectopic amplification is a form of abnormal oncogenes. We propose Hi-C as a screening method for this phenomenon. We will further verify this phenomenon in various phases of multiple AML cell lines and patient samples.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 113-121"},"PeriodicalIF":2.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048474","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}
引用次数: 0
Exploring replication stress and cellular senescence as key targets in novel cancer therapies 探索复制应激和细胞衰老作为新型癌症治疗的关键靶点
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-02 DOI: 10.1016/j.cancergen.2025.09.002
Suman Kumar Ray, Sukhes Mukherjee
{"title":"Exploring replication stress and cellular senescence as key targets in novel cancer therapies","authors":"Suman Kumar Ray,&nbsp;Sukhes Mukherjee","doi":"10.1016/j.cancergen.2025.09.002","DOIUrl":"10.1016/j.cancergen.2025.09.002","url":null,"abstract":"<div><div>The hallmark features most commonly found in human cancers include sustained cell proliferation, evasion of apoptosis, and genetic instability. Replication stress, which contributes to genome instability and is characteristic of both pre-cancerous and cancerous cells, arises from conditions that cause significant DNA damage. DNA replication is a highly controlled process in each cell cycle, ensuring accurate duplication of DNA for distribution to daughter cells. Cellular senescence prevents damaged or aging cells from dividing by halting their progression through the cell cycle. Senescent cells undergo a variety of changes, such as metabolic shifts, chromatin alterations, and autophagy regulation. Senescence can be triggered by telomere shortening, leading to a limited number of cell divisions (replicative senescence), or by oncogene overexpression, which functions as a mechanism to protect against cancer. A number of activated oncogenes have been shown to induce replication stress, a crucial early step in the development of cancer. Investigating the mechanisms behind the replication stress response may open up new avenues for cancer therapies, including small-molecule inhibitors targeting pathways such as Chk1, TLK, WEE1, ATR, MELK, PARP, NAE, and others. This review examines the relationship between persistent replication stress and cellular senescence in carcinogenesis, aiming to provide insights into the early stages of oncogenesis and to inform the development of new cancer diagnostic and therapeutic strategies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 78-87"},"PeriodicalIF":2.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027020","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}
引用次数: 0
Ellagic acid inhibits EZH2: a potential epigenetic therapeutic molecule for cancer 鞣花酸抑制EZH2:一种潜在的癌症表观遗传治疗分子
IF 2.1 4区 医学
Cancer Genetics Pub Date : 2025-09-02 DOI: 10.1016/j.cancergen.2025.09.001
Kirankumar Nalla , Biji Chatterjee , Jagadeesha Poyya , Aishwarya Swain , Krishna Ghosh , Archana Pan , Chandrashekhar G Joshi , Bramanandam Manavathi , Santosh R Kanade
{"title":"Ellagic acid inhibits EZH2: a potential epigenetic therapeutic molecule for cancer","authors":"Kirankumar Nalla ,&nbsp;Biji Chatterjee ,&nbsp;Jagadeesha Poyya ,&nbsp;Aishwarya Swain ,&nbsp;Krishna Ghosh ,&nbsp;Archana Pan ,&nbsp;Chandrashekhar G Joshi ,&nbsp;Bramanandam Manavathi ,&nbsp;Santosh R Kanade","doi":"10.1016/j.cancergen.2025.09.001","DOIUrl":"10.1016/j.cancergen.2025.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Dysregulation of epigenetic processes, characterized by aberrant DNA methylation patterns and histone modifications, is a hallmark of cancer, driving its initiation, progression, and metastasis by silencing tumor suppressor genes or activating oncogenes. Perturbations in histone modifications such as H3K27me3 by EZH2 (Enhancer of Zeste homolog 2) play significant roles in these epigenetic alterations, disrupting normal gene expression and facilitating oncogene activation while suppressing tumor suppressor genes. Consequently, inhibitors targeting enzymes involved in DNA methylation, histone modification, or chromatin remodeling, such as PRC (Polycomb Repressive Complex) complexes, are promising anti-cancer agents, with several undergoing pre-clinical and clinical trials.</div></div><div><h3>Study Design/ Methods</h3><div>The molecular interaction of ellagic acid (EA) with EZH2 was determined by molecular docking using the Schrödinger suite. The binding of EA with EHZ2 was determined by Surface Plasmon Resonance and molecular dynamic simulation studies. In vitro methylation followed by ELISA confirmed the inhibitory potential. Effect of -EA- on the growth and proliferation of the cancer cell lines were determined using the MTT assay. The Ethidium Bromide &amp; Acridine Orange (EB/AO) double staining, colony formation assay, cell cycle and apoptosis assays demonstrated the effect of EA. In vivo mouse xenografts revealed the anticancer potential of EA.</div></div><div><h3>Results</h3><div>Screening of a phytochemical library revealed EA as an effective inhibitor of EZH2. EA interacts strongly with the EZH2, binding to its active sites through π-cation interactions and hydrogen bonds. Molecular dynamic simulation and Surface Plasmon Resonance studies confirmed potent binding affinities of EA, with KD values of 3.28E-06. <em>In-vitro</em> assays validated inhibitory effects on EZH2 by reducing the H3K27me3 levels and induction of autophagy and apoptosis. <em>In- vivo</em> studies using mouse xenografts further demonstrated significant tumor size reductions upon oral administration of EA, with decreased expression of the proliferative marker Ki67 and histone repressive marks.</div></div><div><h3>Conclusion</h3><div>Taken together we showed that inhibition of EZH2 by EA could be used to develop breast cancer therapeutic drug.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 99-112"},"PeriodicalIF":2.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048475","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}
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