Cancer Genetics最新文献_第2页

In silico identification of deleterious NT5C2 and PRPS1 mutations driving thiopurine resistance in relapsed acute lymphoblastic leukemia 恶性nt52c和PRPS1突变驱动复发性急性淋巴细胞白血病硫嘌呤耐药的计算机鉴定

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-04-01 Epub Date: 2026-01-04 DOI: 10.1016/j.cancergen.2026.01.001

Ramita Sharma , Jeeshitha Kudithipudi , Himanshu Singh , Dhamodharan Prabhu , Sugunakar Vuree

{"title":"In silico identification of deleterious NT5C2 and PRPS1 mutations driving thiopurine resistance in relapsed acute lymphoblastic leukemia","authors":"Ramita Sharma , Jeeshitha Kudithipudi , Himanshu Singh , Dhamodharan Prabhu , Sugunakar Vuree","doi":"10.1016/j.cancergen.2026.01.001","DOIUrl":"10.1016/j.cancergen.2026.01.001","url":null,"abstract":"<div><div>Relapse in Acute Lymphoblastic Leukemia (ALL) are often driven by multiple factors, including thiopurine drug-resistant mutations in NT5C2 and PRPS1. To determine the functional significance of these mutations, we employed comprehensive computational methods to assess their impact on protein stability, evolutionary conservation, and possible drug sensitivity, as well as molecular docking and simulations with 6-MP and 6-TG to show the impact of these mutations on drug binding. The top-ranked pathogenic variants investigated, NT5C2 rs775844720 (D431V) and PRPS1 rs2147684832 (D224G), exhibited the most pronounced destabilizing effects on proteins. Protein-protein interaction networks indicate that these variations are involved in nucleotide metabolism and pharmacological responses, confirming their role in thiopurine resistance. In summary, NT5C2 and PRPS1 gene variations may act as potential biomarkers for resistance and hence require more experimental validation of VUS to determine their significance.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 8-12"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941380","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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Functional impact assessment of tissue-specific missense variants in the PTPRH gene using a multi-tool computational framework 使用多工具计算框架评估PTPRH基因中组织特异性错义变异的功能影响。

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-04-01 Epub Date: 2026-01-14 DOI: 10.1016/j.cancergen.2026.01.006

Ali Ammar Naseem , Ranjha Khan , Uzma Hameed

{"title":"Functional impact assessment of tissue-specific missense variants in the PTPRH gene using a multi-tool computational framework","authors":"Ali Ammar Naseem , Ranjha Khan , Uzma Hameed","doi":"10.1016/j.cancergen.2026.01.006","DOIUrl":"10.1016/j.cancergen.2026.01.006","url":null,"abstract":"<div><div>Cancer is driven by genetic alterations that disrupt cellular processes, and one key gene involved in this progression is Protein Tyrosine Phosphatase Receptor Type H (<em>PTPRH</em>). Acting as both a tumor suppressor and oncogene, the role of <em>PTPRH</em> varies across cancer types. Mutations in <em>PTPRH</em> can either promote cancer or act as tumor suppressors, depending on the type of tissue in which they occur. This project investigates missense variants of <em>PTPRH</em> using <em>in silico</em> analysis. From the COSMIC database, 478 unique missense variants were identified, with 14 variants consistently predicted as damaging across eight computational tools (fathmm, PROVEAN, PolyPhen-2, SIFT, PANTHER, Align-GVGD, SNPs&GO, and PhD-SNP). These variants were analyzed for their impact on protein stability using several prediction tools (MUpro, I-Mutant, MCSM, Missense3D, SDM, DUET, DynaMut, and ENCoM), with 10 variants showing potential disruption of <em>PTPRH</em> protein stability. Evolutionary conservation analysis revealed high conservation scores for all 14 variants, indicating the structural importance of these variants. The domain profiling also revealed their location in key regions of the protein. The 3D protein structures were constructed by homology modeling using the Swiss-Model server. Further analysis using GeneMANIA and STRING highlighted the broader impacts of these mutations on <em>PTPRH</em> interactions and cellular pathways. Investigating the association of <em>PTPRH</em> mutations with various cancer types using CanSAR.ai, cBioPortal, Kaplan-Meier Plotter, and GEPIA revealed their significance in cancer progression. These findings emphasize the utility of in silico analysis in prioritizing cancer-associated variants and provide a rational foundation for future experimental validation and targeted therapeutic investigation.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 50-61"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031185","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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Plasma cell-free DNA biomarkers as novel diagnostic and prognostic tools in breast cancer 血浆无细胞DNA生物标志物作为乳腺癌诊断和预后的新工具

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-04-01 Epub Date: 2025-12-24 DOI: 10.1016/j.cancergen.2025.12.004

Rofida M. Abd El-Fatah , Heba K. Badawy , Heba F. Pasha , Noha M. Mesbah , Dina M. Abo-Elmatty , Asmaa R. Abdel-Hamed

{"title":"Plasma cell-free DNA biomarkers as novel diagnostic and prognostic tools in breast cancer","authors":"Rofida M. Abd El-Fatah , Heba K. Badawy , Heba F. Pasha , Noha M. Mesbah , Dina M. Abo-Elmatty , Asmaa R. Abdel-Hamed","doi":"10.1016/j.cancergen.2025.12.004","DOIUrl":"10.1016/j.cancergen.2025.12.004","url":null,"abstract":"<div><div>Breast cancer remains the leading cause of cancer-related deaths among women, underscoring the need for more sensitive and specific biomarkers. Traditional markers such as CA15-3 lack sufficient diagnostic and prognostic accuracy. Quantification of plasma cell-free DNA (cfDNA) offers a minimally invasive liquid-biopsy approach for tumor detection and monitoring. This case–control study assessed a cfDNA panel comprising <em>KLK10, SOX17, WNT5A</em>, and <em>MSH2</em> in 100 breast cancer patients and 100 matched controls. Plasma cfDNA levels, quantified by qPCR, and CA15-3 levels, measured by ELISA, were evaluated for diagnostic and prognostic value using ROC analyses and a 35-month follow-up for survival endpoints. All cfDNA genes were significantly elevated in patients (p<0.001) and exhibited superior diagnostic accuracy versus CA15-3, with <em>MSH2</em> showing the highest AUC (95.3%), sensitivity (92%), and specificity (89%). Elevated cfDNA correlated strongly with metastasis and adverse pathological features, outperforming CA15-3 in predicting metastasis (AUC = 0.962–0.987). High cfDNA concentrations associated with poorer disease-free and overall survival (p<0.001). Detection of a cfDNA panel, rather than a single gene, demonstrates superior utility as a minimally invasive biomarker promising for early detection, risk assessment, and disease monitoring in breast cancer.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 1-7"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908866","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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M6A methylation in thyroid cancer: Functions, mechanisms, and clinical significance 甲状腺癌中M6A甲基化：功能、机制和临床意义

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-04-01 Epub Date: 2026-01-10 DOI: 10.1016/j.cancergen.2026.01.005

Dongye Huang , Zhuoya Xie , Senmin Zhang , Yaorong Su , Chang Liu , Wenkuan Chen

{"title":"M6A methylation in thyroid cancer: Functions, mechanisms, and clinical significance","authors":"Dongye Huang , Zhuoya Xie , Senmin Zhang , Yaorong Su , Chang Liu , Wenkuan Chen","doi":"10.1016/j.cancergen.2026.01.005","DOIUrl":"10.1016/j.cancergen.2026.01.005","url":null,"abstract":"<div><div>Thyroid cancer (TC), the most prevalent endocrine malignancy, exhibits marked biological heterogeneity and a persistent therapeutic gap in aggressive, treatment-refractory subsets. N6-methyladenosine (m6A), pervasive across eukaryotic RNA processing—splicing, maturation, stability, translation, and localization—constitutes a central layer of epigenetic regulation. By reshaping post-transcriptional programs, m6A modifications govern tumor initiation and progression, sustaining stemness, accelerating proliferation and invasion, and mediating therapy resistance. A growing body of evidence implicates dysregulated m6A regulators in TC pathogenesis; yet the multiplicity of effectors and their context-dependent actions complicate mechanistic resolution. This review synthesizes current advances, delineating m6A’s involvement in four cardinal arenas of thyroid tumorigenesis: altered cellular behaviors (proliferation, migration), metabolic reprogramming, programmed cell death (apoptosis and ferroptosis), and resistance to targeted, radioactive iodine, and immunotherapeutic strategies. We further examine the emerging interface between m6A and non-coding RNAs, highlighting how this axis rewires oncogenic networks. Finally, we appraise the translational potential of m6A as a diagnostic and prognostic biomarker and as a therapeutic target, offering perspective on opportunities and challenges for epitranscriptome-guided precision oncology in TC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 27-39"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980932","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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Investigation of hnRNPK's role in gastric cancer proliferation and migration and its interaction with TL1A hnRNPK在胃癌增殖和迁移中的作用及其与TL1A相互作用的研究

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.cancergen.2026.01.004

Sihan Bo , Tao Jiang , Yong You , Shuang Tian , Bing Bai , Yu Cheng , Yaxian Gao , Yongwei Wang

{"title":"Investigation of hnRNPK's role in gastric cancer proliferation and migration and its interaction with TL1A","authors":"Sihan Bo , Tao Jiang , Yong You , Shuang Tian , Bing Bai , Yu Cheng , Yaxian Gao , Yongwei Wang","doi":"10.1016/j.cancergen.2026.01.004","DOIUrl":"10.1016/j.cancergen.2026.01.004","url":null,"abstract":"<div><div>The present investigation elucidated the pivotal involvement of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in the oncogenic advancement of gastric carcinoma through an integrative, multi-tiered analytical framework. Quantitative tissue microarray assessments indicated that elevated hnRNPK abundance exhibited a marked association with tumor differentiation grade, lymphatic dissemination, TNM classification, and unfavorable clinical outcome. Mechanistic exploration further substantiated that hnRNPK, predominantly confined to the nuclear compartment, facilitates gastric tumor aggressiveness by modulating the PI3K/Akt transduction cascade. Both in vivo and in vitro assays consistently verified that hnRNPK markedly augments the proliferative and motile potentials of gastric carcinoma cells. Importantly, this research constitutes the initial report delineating a molecular linkage between hnRNPK activity and gastric cancer pathogenesis. Rescue experiments demonstrated that TL1A knockdown in hnRNPK-overexpressing cells significantly reversed pro-tumor phenotypes, suggesting that hnRNPK exerts its oncogenic effects at least partially through a TL1A-dependent mechanism. These findings not only provide insights into the molecular mechanism of hnRNPK in GC but also offer experimental evidence for developing novel therapeutic strategies targeting the hnRNPK-TL1A axis in GC.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"302 ","pages":"Pages 40-49"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980915","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

Single-Step CRISPR/Cas13a Assay for detection of small RNAs in Saliva : a proof-of-concept study 单步CRISPR/Cas13a检测唾液中小rna：一项概念验证研究

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-01-01 Epub Date: 2025-12-12 DOI: 10.1016/j.cancergen.2025.12.003

Devyani Salodkar , Sheetal Dongarwar , Aparna Nair , Prajkta Ashtaputre , Shreya Reddy , Shrutam Somkuwar , Deovrat Begde

{"title":"Single-Step CRISPR/Cas13a Assay for detection of small RNAs in Saliva : a proof-of-concept study","authors":"Devyani Salodkar , Sheetal Dongarwar , Aparna Nair , Prajkta Ashtaputre , Shreya Reddy , Shrutam Somkuwar , Deovrat Begde","doi":"10.1016/j.cancergen.2025.12.003","DOIUrl":"10.1016/j.cancergen.2025.12.003","url":null,"abstract":"<div><h3>Objective</h3><div>We describe a proof-of-concept study of a rapid, single-step CRISPR/Cas13a assay using <em>Leptotrichia wadei</em> (LwCas13a) for the detection of small RNA (miRNA) biomarkers in saliva, and compare its performance to real-time PCR (RT-PCR).</div></div><div><h3>Methods</h3><div>The single-step Cas13a assay was evaluated against RT-PCR for its detection efficiency, sensitivity, specificity, and its ability to function in a complex biological matrix. A proof-of-concept test was conducted on patient saliva samples to detect a known oral cancer biomarker, hsa-miR-21–3p</div></div><div><h3>Results</h3><div>The Cas13a assay successfully detected candidate miRNA at picomolar concentrations in both in vitro and saliva samples, demonstrating sensitivity and specificity comparable to RT-PCR. Notably, the assay provided discernible detection of the cancer biomarker directly in patient saliva without the need for RNA extraction or reverse transcription steps.</div></div><div><h3>Conclusion</h3><div>The proposed single-step CRISPR/Cas13a assay may be developed into a promising platform for developing quick and affordable point-of-care diagnostics for cancer and other diseases, circumventing the need for expensive and time-consuming sample preparation steps.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"300 ","pages":"Pages 67-71"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797585","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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Genetic modulation of ABCB1: Sunvozertinib reverses ABCB1-mediated multidrug resistance in cancer cells ABCB1的遗传调控：Sunvozertinib逆转ABCB1介导的癌症细胞多药耐药。

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-01-01 Epub Date: 2025-12-02 DOI: 10.1016/j.cancergen.2025.12.001

Lu-Qi Cao , Yuhao Xie , Xuanyu Chen , Harsh Patel , Luoxi Yuan , John Wurpel , Kunxiang Gong , Zhe-Sheng Chen

{"title":"Genetic modulation of ABCB1: Sunvozertinib reverses ABCB1-mediated multidrug resistance in cancer cells","authors":"Lu-Qi Cao , Yuhao Xie , Xuanyu Chen , Harsh Patel , Luoxi Yuan , John Wurpel , Kunxiang Gong , Zhe-Sheng Chen","doi":"10.1016/j.cancergen.2025.12.001","DOIUrl":"10.1016/j.cancergen.2025.12.001","url":null,"abstract":"<div><div>Sunvozertinib is an oral, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) designed to treat non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations under a phase II clinical trial. In this study, we investigated whether sunvozertinib could antagonize ABCB1, also known as multidrug resistance 1 (MDR1/P-gp). ABCB1 is a gene that encodes an important drug transport protein that pumps various substances, including drugs and toxins, out of cells. Sunvozertinib received a high score in docking analysis, indicating a strong interaction between sunvozertinib and ABCB1. ATPase assay indicated that sunvozertinib stimulated ABCB1 ATPase activity in a concentration-dependent manner. MTT assay shows that sunvozertinib significantly reversed ABCB1-mediated MDR but not ABCC1- and ABCG2-mediated MDR. Mechanistic studies show that sunvozertinib significantly reversed ABCB1-mediated MDR by attenuating the efflux activity of the ABCB1 transporter. Furthermore, treatment with sunvozertinib did not change protein expression or subcellular localization of ABCB1. Altogether, these data demonstrate that sunvozertinib, when combined with other conventional chemotherapeutic agents, can overcome MDR and improve therapeutic effect.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"300 ","pages":"Pages 47-57"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745526","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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Corrigendum to “Study on the Anticancer Mechanism of Hydroxygenkwanin in Esophageal Cancer via the ESRRA Signaling Pathway” [Cancer Genetics, 298–299, (2025) Pages 180-192] “羟基根wanin在食管癌中ESRRA信号通路的抗癌机制研究”的勘误表[Cancer Genetics， 298-299, (2025) page 180-192]。

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-01-01 Epub Date: 2025-11-29 DOI: 10.1016/j.cancergen.2025.11.009

Yuan Wang , Li XinWan , Yutian Zhang , Qi Jia , Chao Li , Xiaonan Cui

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Exploration of a prognostic model for childhood acute lymphoblastic leukemia 儿童急性淋巴细胞白血病预后模型的探讨。

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-01-01 Epub Date: 2025-12-09 DOI: 10.1016/j.cancergen.2025.12.002

Yu Bai , Wen-wen Feng , Lan Tang , Yan-qing Sun

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Quantitative and qualitative methods for measuring chromosomal instability in tumor cells 测定肿瘤细胞染色体不稳定性的定量和定性方法。

IF 2.1 4区医学

Cancer Genetics Pub Date : 2026-01-01 Epub Date: 2025-11-24 DOI: 10.1016/j.cancergen.2025.11.008

Hanna Karolina de Araújo Batistão , João Marcos Oliveira-Silva , Vinícius Bernardo Oliveira , Isaac Iogan de Araújo Batistão , Angel Mauricio Castro-Gamero

{"title":"Quantitative and qualitative methods for measuring chromosomal instability in tumor cells","authors":"Hanna Karolina de Araújo Batistão , João Marcos Oliveira-Silva , Vinícius Bernardo Oliveira , Isaac Iogan de Araújo Batistão , Angel Mauricio Castro-Gamero","doi":"10.1016/j.cancergen.2025.11.008","DOIUrl":"10.1016/j.cancergen.2025.11.008","url":null,"abstract":"<div><div>To preserve cellular and tissue homeostasis, cells must maintain a coordinated network of molecular mechanisms that ensure accurate chromosome segregation during mitosis. Errors in this process, such as chromosome mis-segregation, lagging chromosomes in anaphase, centrosome amplification, or chromosome breaks generating non-homologous fusions and dicentric chromosomes, can lead to chromosomal instability (CIN). Persistent CIN promotes chromosomal abnormalities, driving tumor cell proliferation, intratumoral genomic diversity, and ultimately tumor initiation and progression. Tumors exhibiting CIN, characterized by aneuploidy or large-scale structural rearrangements, are strongly associated with metastasis, angiogenesis, and chemoresistance. Despite its biological and clinical relevance, methods to detect, quantify, and evaluate CIN remain poorly standardized. In this work, we critically reviewed the scientific literature to compile and discuss the principal quantitative and qualitative strategies currently available for measuring CIN <em>in vitro</em>.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"300 ","pages":"Pages 36-46"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688612","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