Cancer Genetics最新文献

{"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}

{"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}

{"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}

{"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}

{"title":"Genetic silencing of CDC6 via AAV2-Delivered shRNA as a novel cancer genetics-based therapy for cervical carcinoma.","authors":"Yajie Wang, Xiaofeng Li, Xiaoying Lian, Baihai Huang, Jing Jia, Changjun Zhu","doi":"10.1016/j.cancergen.2025.08.001","DOIUrl":"10.1016/j.cancergen.2025.08.001","url":null,"abstract":"<p><strong>Background: </strong>Cell division cycle 6 (Cdc6) is an oncogenic driver in cervical cancer, whose dysregulation accelerates S-phase entry and promotes genomic instability. As a key replication licensing factor, its overexpression creates a cancer-specific vulnerability, making it a promising therapeutic target.</p><p><strong>Objective: </strong>To evaluate whether silencing Cdc6 via an adeno-associated virus serotype 2 (AAV2)-delivered shRNA can selectively inhibit cervical cancer growth while sparing normal cells.</p><p><strong>Methods: </strong>We constructed an AAV2 vector encoding short hairpin RNA (shRNA) targeting Cdc6 and validated its efficacy in vitro using multiple cervical cancer cell lines and an immortalized epithelial cell line (HaCaT). Functional assays assessed cell cycle progression, apoptosis, and DNA damage. Antitumor efficacy was further assessed in xenograft mouse models.</p><p><strong>Results: </strong>AAV2-shCdc6 transduction efficiently silenced Cdc6 expression, leading to G2/M phase arrest, increased γ-H2AX expression, and significant apoptosis in cervical cancer cells. In contrast, normal HaCaT cells exhibited only S-phase arrest without apoptosis. In vivo, AAV2-shCdc6 treatment significantly inhibited tumor growth in xenograft models without observable systemic toxicity.</p><p><strong>Conclusion: </strong>AAV2-mediated Cdc6 knockdown selectively targets cervical cancer by exploiting a defined genetic vulnerability. This cancer genetics-based strategy offers a precise and well-tolerated approach for cervical cancer therapy.</p>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"296-297 ","pages":"208-216"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800704","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":"Comprehensive analysis of oncogenic determinants across tumor types via multi-omics integration","authors":"Saba Ubaid ,&nbsp;Rashmi Kushwaha ,&nbsp;Mohammad Kashif ,&nbsp;Vivek Singh","doi":"10.1016/j.cancergen.2025.08.010","DOIUrl":"10.1016/j.cancergen.2025.08.010","url":null,"abstract":"<div><div>Cancer is a complex and heterogeneous disease characterized by the accumulation of genetic and epigenetic alterations that drive uncontrolled cellular proliferation and survival. This review provides a comprehensive overview of key cancer driver genes, including oncogenes such as <em>KRAS</em> and <em>PIK3CA</em>, as well as tumor suppressor genes like <em>TP53, PTEN</em>, and <em>CDKN2A</em>, highlighting their molecular mechanisms and roles across various types of cancer. Leveraging insights from large-scale cancer genome initiatives and whole-genome sequencing, we examine the landscape of somatic mutations and their association with hallmark cancer pathways, including cell cycle regulation, apoptosis, metabolic reprogramming, and immune evasion. Multi-omics integration—encompassing genomic, transcriptomic, proteomic, and epigenomic data has enabled the identification of novel driver mutations, functional interactions, and tumor-specific vulnerabilities. We explore bioinformatics platforms, such as IntOGen, that facilitate the detection and prioritization of driver genes and discuss emerging concepts, including synthetic lethality, chromatin remodeling defects, and epigenetic dysregulation, involving genes like <em>ARID1A, KMT2D</em>, and <em>RB1</em>. Furthermore, we review therapeutic strategies targeting these molecular aberrations, including small-molecule inhibitors, pathway-based therapies, and precision oncology approaches guided by biomarkers. This synthesis underscores the importance of integrating multidimensional data to enhance our understanding of cancer biology and refine personalized treatment strategies for improved patient outcomes.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 44-62"},"PeriodicalIF":2.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996293","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 role of miR-10b-5p in prostate cancer and its exosome-mediated angiogenesis effect","authors":"Jia Wang ,&nbsp;Chuan Zhou ,&nbsp;Qi-dong Wang ,&nbsp;Wen-bo Zhang ,&nbsp;Chao Wang ,&nbsp;Yun-Feng Zhang ,&nbsp;Hao-Xuan Lv ,&nbsp;Feng-Hai Zhou","doi":"10.1016/j.cancergen.2025.08.009","DOIUrl":"10.1016/j.cancergen.2025.08.009","url":null,"abstract":"<div><h3>Objective</h3><div>Prostate cancer (PCa) continues to be a major cause of cancer-related mortality globally, underscoring the critical need for novel therapeutic strategies. This study investigates the oncogenic function of miR-10b-5p in PCa progression and evaluates its potential as both a diagnostic marker and therapeutic target.</div></div><div><h3>Methods</h3><div>miR-10b-5p was initially identified as a candidate oncogene through bioinformatic analysis of The Cancer Genome Atlas (TCGA) PCa data, followed by validation of its expression levels in clinical PCa specimens via fluorescence in situ hybridization (FISH). Functional assays (proliferation, migration, invasion) were performed to assess the impact of miR-10b-5p on PCa cell behavior. The tumor suppressor ZMYND11 was confirmed as a direct target of miR-10b-5p using dual-luciferase reporter assays. The pro-angiogenic capacity of PCa-derived exosomes harboring miR-10b-5p was evaluated using in vitro endothelial tube formation assays and in vivo mouse models.</div></div><div><h3>Results</h3><div>miR-10b-5p expression was significantly elevated in PCa tissues and cell lines, and its levels correlated with aggressive tumor features. Mechanistically, miR-10b-5p directly suppressed ZMYND11 expression, thereby promoting PCa cell proliferation, migration, and invasion. Crucially, exosomes derived from miR-10b-5p-expressing PCa cells exhibited potent pro-angiogenic activity, significantly enhancing endothelial tube formation in vitro and stimulating tumor neovascularization in vivo.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that miR-10b-5p promotes prostate cancer progression by targeting ZMYND11, while its exosomes additionally exhibit pro-angiogenic effects, providing a novel therapeutic target for clinical intervention.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 27-38"},"PeriodicalIF":2.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926173","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":"Dramatic multifocal osteosarcoma treatment response in the setting of POT1 tumor predisposition syndrome","authors":"Stephen Gilene ,&nbsp;Kristen D'Aquila ,&nbsp;Brittany Cooper ,&nbsp;Sara Szabo ,&nbsp;Joseph G. Pressey","doi":"10.1016/j.cancergen.2025.08.008","DOIUrl":"10.1016/j.cancergen.2025.08.008","url":null,"abstract":"<div><div>INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is associated with a spectrum of malignancies due to loss of function mutations in <em>POT1</em> leading to telomere elongation and genomic instability. Osteosarcoma is the most common primary malignant bone tumor and has a poor prognosis when multifocal. CASE PRESENTATION: A 15-year-old male was found to have a primary right distal femur osteosarcoma with multiple additional bony sites of disease. A <em>POT1</em> splice site variant (c.949+1G&gt;C) was identified both somatically and in the germline consistent with POT1-TPD. Despite extensive multifocality, the tumor displayed marked chemosensitivity to standard of care therapy and long-term remission was achieved. DISCUSSION: Evidence suggests that hereditable alterations in telomeric function including <em>POT1</em> are enriched in sarcoma susceptibility. Furthermore, hereditary tumor predisposition syndromes often increase osteosarcoma risk including a recent report of five patients with POT1-TPD. Multifocal osteosarcoma is rare, but a few retrospective cohorts suggest dismal prognosis. This report details an adolescent male with presumed POT1-TPD who developed synchronous multifocal osteosarcoma exquisitely sensitive to chemotherapy which may represent a unique phenotype for the syndrome.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 39-43"},"PeriodicalIF":2.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933067","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":"Unraveling complex karyotype clonal architecture: co-existing double TP53 mutations alongside DNMT3A, TET2, and NF1 mutations – a case study","authors":"Suhaib Mohammad Ali Abunaser ,&nbsp;Anurita Pais ,&nbsp;Manu Venkatesan ,&nbsp;Uzma Zaidi ,&nbsp;Cigdem Pala Ozturk","doi":"10.1016/j.cancergen.2025.08.007","DOIUrl":"10.1016/j.cancergen.2025.08.007","url":null,"abstract":"<div><div>Complex chromosomal changes in Acute Myeloid Leukemia (AML) are highly heterogeneous, with disease progression shaped by both the number and nature of abnormalities. Rarely do, multiple unrelated clones with independent chromosomal changes coexist at diagnosis.</div><div>Present study showcases a comprehensive characterization of two cytogenetically distinct complex clones in AML, driven by non-cyclic and chromoplexy mechanisms, highlighting their co-existence with key molecular alterations (<em>TP53, NF1, DNMT3A, TET2</em>) along with their potential contribution to clonal evolution.</div><div>In the present study a refined assessment of clonal chromosomal complexity is provided, with each clone exhibiting distinct alterations involving chromosomes 5, 14, and 17 along with variant structural formation of chromosomes ie. isochromosome 5p, partial monosomy 7 and derivative 17, defining the heterogeneity of clonal architecture.</div><div>Additionally, we propose a probable association between mutational burden and chromosomal complexity, as evidenced by the coexistence of distinct clones with varying mutation loads and cytogenetic profiles, reflecting parallel clonal evolution.</div><div>Our integrated approach combining karyotyping and fluorescence <em>in situ</em> hybridization (FISH) was essential in unraveling the clonal architecture, providing valuable insights into the personalized chromosomal alterations and pathogenetic mechanisms that would be helpful for refining prognosis and guiding AML management.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 63-68"},"PeriodicalIF":2.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018563","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":"A novel fumarate hydratase frameshift mutation in lung adenocarcinoma: A case report","authors":"Haruko Nakagawa ,&nbsp;Satoru Aoyama ,&nbsp;Junko Yokobori ,&nbsp;Haruhiko Furusawa ,&nbsp;Takahiro Mitsumura ,&nbsp;Akira Takemoto ,&nbsp;Ken Yamagiwa ,&nbsp;Masaaki Kawanishi ,&nbsp;Yasunari Miyazaki ,&nbsp;Sadakatsu Ikeda","doi":"10.1016/j.cancergen.2025.08.006","DOIUrl":"10.1016/j.cancergen.2025.08.006","url":null,"abstract":"<div><div>Fumarate hydratase (<em>FH</em>) is a tumor suppressor gene implicated in the tumorigenesis of several cancers, including renal cell carcinoma. However, <em>FH</em> mutations are uncommon in lung adenocarcinoma, and frameshift deletions are exceedingly rare. Here, we report a novel <em>FH</em> frameshift mutation (G97fs*3) in a 67-year-old woman with lung adenocarcinoma. The mutation was detected through comprehensive genomic profiling. It occurs within the catalytic domain of FH and has not been previously reported in this cancer type. A literature review revealed that <em>FH</em> mutations are oncogenic in hereditary leiomyomatosis and renal cell cancer, suggesting that the frameshift mutation could also serve as a driver mutation in this case. This report highlights the utility of comprehensive genomic profiling in identifying clinically relevant mutations and demonstrates the potential of leveraging such insights for precision oncology. <em>FH</em> alterations, such as the one described, could represent potential therapeutic targets from molecular perspectives.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"298 ","pages":"Pages 16-19"},"PeriodicalIF":2.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144878618","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}