Cancer Genetics[JOURNAL]
Sun
200 papers
RNF121 promotes the proliferation, migration, and invasion of lung cancer cell lines.
Jiang J, Chen X, Dong X … +6 more , Wang Y, Liu J, Liu T, Bian X, Li M, Liu Y
Cancer Genet · 2025 Nov · PMID 41092854 · Publisher ↗
OBJECTIVES: RING finger proteins are a large family of proteins within the human genome that play essential roles in the regulation of physiological processes and have been implicated in cancer progression. However, the...
OBJECTIVES: RING finger proteins are a large family of proteins within the human genome that play essential roles in the regulation of physiological processes and have been implicated in cancer progression. However, the relationships among RING Finger Protein 121 (RNF121), E3 ubiquitin ligase, and tumorigenesis have yet to be determined. In this study, we aimed to comprehensively elucidate the functions of RNF121 in non-small cell lung cancer (NSCLC). METHODS: On the basis of MTT, colony formation, and Transwell assays, we evaluated RNF121-specific functions that were found to be closely associated with clinicopathological features. RESULTS: RNF121 expression was demonstrated to be closely associated with different diseases. By altering the levels of this protein in the A549 and H1299 cell lines, we discovered that this protein promotes cell proliferation, migration, and invasion. CONCLUSION: This study is the first to demonstrate that RNF121 plays a prominent role in driving NSCLC progression and that its expression is correlated with clinicopathological features. Accordingly, this gene would serve not only as a key prognostic indicator but also as a novel potential therapeutic target for the treatment of NSCLC.
Study on the anticancer mechanism of hydroxygenkwanin in esophageal cancer via the ESRRA signaling pathway.
Wang Y, Xin Wan L, Zhang Y … +3 more , Jia Q, Li C, Cui X
Cancer Genet · 2025 Nov · PMID 41092853 · Publisher ↗
OBJECTIVE: To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying mol...
OBJECTIVE: To explore the role of ESRRA in esophageal squamous cell carcinoma (ESCC) progression and evaluate the antitumor effects of hydroxygenkwanin (HGK), focusing on its interaction with ESRRA and the underlying molecular mechanisms. METHODS: Cell viability, apoptosis, invasion, and proliferation were assessed in EC109 and TE-1 cells treated with HGK using CCK-8, Hoechst staining, Transwell, and colony formation assays. ESRRA expression was analyzed via qPCR and Western blot. An ESCC mouse model was established, with treatment groups receiving HGK. Serum IL-10 and IL-12 levels were measured by ELISA; tumor growth and toxicity were evaluated by histology. EMT marker expression was analyzed by IHC and RT-qPCR. TCGA database analysis explored ESRRA-related pathways and its link to the tumor microenvironment and patient survival. RESULTS: HGK inhibited EC109 and TE-1 cell proliferation and migration, especially in EC109 cells, by downregulating ESRRA in a dose-dependent manner. In vivo, HGK reduced tumor growth with minimal toxicity, though high doses showed possible renal effects. IL-12 levels decreased, and EMT markers were altered. ESRRA was overexpressed in ESCC tissues and correlated with EMT-related genes. TCGA analysis confirmed ESRRA's association with poor survival in ESCC patients. CONCLUSION: HGK effectively suppresses ESCC with low toxicity, primarily by inhibiting ESRRA and blocking EMT, highlighting its therapeutic potential.
Influence of lynch syndrome on the incidence of side effects to antineoplastic treatment of patients with colorectal cancer.
Alencar AVS, Barreto GAV, Luciano MCDS … +6 more , Albuquerque CP, de Sant'Ana RO, Silva PGB, Bittencourt FDS, Lima VP, Bezerra MJB
Cancer Genet · 2025 Nov · PMID 41082795 · Publisher ↗
To analyze the influence of Lynch Syndrome on the incidence of adverse reactions to antineoplastic treatment in patients with colorectal cancer. Observational and retrospective study based on analyzing electronic medical...
To analyze the influence of Lynch Syndrome on the incidence of adverse reactions to antineoplastic treatment in patients with colorectal cancer. Observational and retrospective study based on analyzing electronic medical records of patients treated at Hospital Haroldo Juaçaba/Ceará Cancer Institute (HHJ/ICC). Patients with NCCN clinical criteria for Lynch Syndrome and a diagnosis of colorectal cancer were included, comparing the profile of adverse reactions to chemotherapy between those with and without pathogenic mutations associated with the syndrome. The sample consisted of 161 patients with suspected Lynch Syndrome, all undergoing chemotherapy. A higher frequency of adverse reactions was observed among patients without a pathogenic mutation for Lynch Syndrome. Approximately two-thirds of the sample reported adverse reactions, with nausea being the most common adverse event, followed by neurotoxicity and diarrhea. Patients with colorectal cancer without a pathogenic mutation for Lynch syndrome had a higher incidence of adverse reactions to chemotherapy. This finding may be related to biological and physiological factors, including greater cellular variability, the need for more intensive therapeutic regimens, and the influence of individual genetic variability. These results highlight the importance of personalized approaches in managing the side effects of cancer treatment.
Identification of novel gene fusions in high-grade serous ovarian carcinoma: implications for tumorigenesis and targeted therapy.
Masago K, Sasaki E, Fujita Y … +9 more , Fujita S, Horio Y, Kuroda H, Ogasawara A, Tatsuno K, Aburatani H, Oda K, Hasegawa K, Matsushita H
Cancer Genet · 2025 Nov · PMID 41072140 · Publisher ↗
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) accounts for 70% of all ovarian cancer cases and 80% of related deaths. TP53 mutations are common; however, other driving genetic factors are not well understood. I...
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) accounts for 70% of all ovarian cancer cases and 80% of related deaths. TP53 mutations are common; however, other driving genetic factors are not well understood. In this study, we used RNA sequencing to explore the genetic background of HGSOC in patients with unclear profiles. METHODS: This study included 80 patients with a pathological diagnosis of HGSOC. RNA sequencing was performed to analyze gene expression and detect fusion. RESULTS: We identified 18 novel potential driver fusion gene candidates, including in-frame and frameshift fusions, in 80 patients with high-grade serous ovarian cancer (HGSOC). Of these, ST7-OT4::MET, STK24::DOCK9, GAB::PAK1, HDAC1::LCK, ESR1::LATS1, ZNF157::CDK16, NEK7::RP11-85M11.2, CAMKK1::R2RX1, HNRNPUL1::AXL, DYRK1A::GART, MAPKAPK2::DYRK3, and FER::GS1421I3.2 involved fusion partners harboring protein kinase domains. Notably, TAOK1::PIPOX and PSMD11::NLK were identified in the same case, similar to SH3PXD2A::BMPR1A and EIF3H::CAMK2D in another case. In addition, SLMAP::NTRK3 involves NTRK3, a known fusion partner. The remaining fusions, SWAP70::ZNF143, WDR25::YY1, and NR2F6::MYO9B, included partners with DNA-binding domains. CONCLUSIONS: This study identified candidate driver fusion genes and suggested new therapeutic targets for HGSOCs.
Comparison of somatic variant oncogenicity classification using ClinGen/CGC/VICC guidelines and QIAGEN Clinical Insight Interpret decision support software.
Goverdhan A, Mullineaux L, Pryzbylski A … +4 more , Teigen C, Halling KC, Elkin SK, Pitel BA
Cancer Genet · 2025 Nov · PMID 41014803 · Publisher ↗
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 indepen...
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.
Galectin-9 promotes colon cancer development by polarizing macrophages toward the M2 phenotype.
Zhang J, Xu Y, Han X … +3 more , Gao Y, Wei Z, Sun X
Cancer Genet · 2025 Nov · PMID 41005040 · Publisher ↗
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...
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.
Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients.
Yang W, Xu J, Cao S … +11 more , Wang N, Hao Z, Wang Q, Tan Y, Chen X, Xu Z, Zhang Y, Chang J, Wang X, Ren F, Wang H
Cancer Genet · 2025 Nov · PMID 40991983 · Publisher ↗
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...
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 (P = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008-3.792, P = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (P = .013 and P = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (P < .05). 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.
Molecular mechanisms underlying the oncogenic and tumor-suppressive roles of ZHX2 in cancers.
Wei Y, Guo H, Zhou J … +2 more , Shi D, Hao L
Cancer Genet · 2025 Nov · PMID 40991982 · Publisher ↗
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...
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.
The multidimensional role of laminin γ2 (LAMC2) on cancer progression.
Zhang X, Xie J, Fu T … +3 more , Gao Z, Liu H, Yang Z
Cancer Genet · 2025 Nov · PMID 40986946 · Publisher ↗
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 revi...
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.
Ellagic acid inhibits EZH2: a potential epigenetic therapeutic molecule for cancer.
Nalla K, Chatterjee B, Poyya J … +6 more , Swain A, Ghosh K, Pan A, Joshi CG, Manavathi B, Kanade SR
Cancer Genet · 2025 Nov · PMID 40944978 · Publisher ↗
BACKGROUND: 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 t...
BACKGROUND: 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. STUDY DESIGN/ METHODS: 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 & 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. RESULTS: 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. In-vitro assays validated inhibitory effects on EZH2 by reducing the H3K27me3 levels and induction of autophagy and apoptosis. In- vivo 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. CONCLUSION: Taken together we showed that inhibition of EZH2 by EA could be used to develop breast cancer therapeutic drug.
Hi-C analysis of amplification of MYC, PVT1, and CCDC26 on marker chromosomes in the NB-4 cell line.
Kobayashi T, Matsushima S, Ohnishi H
Cancer Genet · 2025 Nov · PMID 40944977 · Publisher ↗
MYC 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 MYC amplification have not been fully...
MYC 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 MYC amplification have not been fully elucidated. To characterize the location of MYC and its surrounding structure in NB-4 cells, we conducted this study using in situ high-throughput chromosomal conformation capture (in situ Hi-C). Hi-C analysis was performed in NB-4 cell line. Whole genome sequencing (WGS) and fluorescence in situ hybridization (FISH) were used for confirmation. Hi-C revealed an inversion involving PVT1 and CCDC26 and amplified segments involving MYC, PVT1, and CCDC26 on 8q24.21 region. MYC, PVT1, and CCDC26 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 MYC, PVT1, and CCDC26 on the two normal chromosomes 8 and multiple marker chromosomes. Our results suggest that the numerical and structural abnormalities of chromosome 8 precede MYC amplification and moving. MYC may have properties that move not only to dmins, but also to other chromosomes such as marker chromosomes for unknown but certain reasons. MYC 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.
Development and multi-cohort validation of a prognostic risk score model for oral squamous cell carcinoma based on a three-gene signature.
Chen J, Kim D, Kim JY … +1 more , Kim HJ
Cancer Genet · 2025 Nov · PMID 40939315 · Publisher ↗
BACKGROUND: Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care. METHODS: Transcr...
BACKGROUND: Oral squamous cell carcinoma (OSCC) carries substantial mortality despite surgery-based management. Reliable biomarkers and practical prognostic tools are needed to guide individualized care. METHODS: 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. RESULTS: The three-gene signature (CXCL12, PLAU, PXDN) 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 p = 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 p ≤ 0.05), with a consistent trend in stage I/II (p = 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. CONCLUSION: 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.
Exploring replication stress and cellular senescence as key targets in novel cancer therapies.
Ray SK, Mukherjee S
Cancer Genet · 2025 Nov · PMID 40934728 · Publisher ↗
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 character...
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.
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.
Kwon GY, Lee S, Hong J … +10 more , Kim Y, Choi HJ, Yun J, Park J, Jung J, Yoon J, Baik S, Lee MK, Lee KR, Kim JW
Cancer Genet · 2025 Nov · PMID 40929787 · Publisher ↗
BACKGROUND: 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 c...
BACKGROUND: 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. METHODS: 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). RESULTS: 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 % (n = 44). Of these HGSC patients, 72.7 % (n = 32) were HRD-positive, including 15 with BRCA1/2 mutations (34.1 %) and 27 with GI-positive (61.4 %). In HGSC, HRD-positive status was associated with solid, pseudoendometrioid or transitional (SET) pattern (P = 0.015). Patients with positive HRD and high GII (>4.2) exhibited improved disease-free survival (DFS) and overall survival (OS) compared to those with negative HRD (P = 0.003 and 0.024, respectively) and low GII (P < 0.001 and P = 0.006, respectively). Multivariate analysis revealed a high GII as a better prognostic indicator for DFS and OS (P = 0.003 and 0.032, respectively). CONCLUSION: 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.
Unraveling complex karyotype clonal architecture: co-existing double TP53 mutations alongside DNMT3A, TET2, and NF1 mutations - a case study.
Abunaser SMA, Pais A, Venkatesan M … +2 more , Zaidi U, Ozturk CP
Cancer Genet · 2025 Nov · PMID 40925076 · Publisher ↗
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...
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. 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 (TP53, NF1, DNMT3A, TET2) along with their potential contribution to clonal evolution. 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. 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. Our integrated approach combining karyotyping and fluorescence in situ 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.
Comprehensive analysis of oncogenic determinants across tumor types via multi-omics integration.
Ubaid S, Kushwaha R, Kashif M … +1 more , Singh V
Cancer Genet · 2025 Nov · PMID 40914134 · Publisher ↗
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 over...
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 KRAS and PIK3CA, as well as tumor suppressor genes like TP53, PTEN, and CDKN2A, 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 ARID1A, KMT2D, and RB1. 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.
Dramatic multifocal osteosarcoma treatment response in the setting of POT1 tumor predisposition syndrome.
Gilene S, D'Aquila K, Cooper B … +2 more , Szabo S, Pressey JG
Cancer Genet · 2025 Nov · PMID 40902353 · Publisher ↗
INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is associated with a spectrum of malignancies due to loss of function mutations in POT1 leading to telomere elongation and genomic instability. Osteosarcoma is the most...
INTRODUCTION: POT1 tumor predisposition (POT1-TPD) is associated with a spectrum of malignancies due to loss of function mutations in POT1 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 POT1 splice site variant (c.949+1G>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 POT1 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.
The role of miR-10b-5p in prostate cancer and its exosome-mediated angiogenesis effect.
Wang J, Zhou C, Wang QD … +5 more , Zhang WB, Wang C, Zhang YF, Lv HX, Zhou FH
Cancer Genet · 2025 Nov · PMID 40902352 · Publisher ↗
OBJECTIVE: 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-...
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Unfavorable disease progression in patients with chronic myeloid leukemia and concurrent t(6;9) translocation (DEK::NUP214 fusion) or inversion 16 (CBFB::MYH11 fusion).
Zhang Y, Reid J, Jeyakumar D … +7 more , Semenova K, Kiran N, Lee L, Fleishman A, Rezk S, Zhao X, Quintero-Rivera F
Cancer Genet · 2025 Nov · PMID 40882571 · Publisher ↗
The occurrence of additional specific chromosomal abnormalities in Philadelphia chromosome-positive (pH+) cells is associated with disease progression in chronic myeloid leukemia (CML), and is considered a marker that de...
The occurrence of additional specific chromosomal abnormalities in Philadelphia chromosome-positive (pH+) cells is associated with disease progression in chronic myeloid leukemia (CML), and is considered a marker that defines the accelerated/blast phase of CML. Both DEK::NUP214 fusion and CBFB rearrangement are extremely rare in CML, and their prognostic significance is unknown. Here we present two CML cases, with one case having concurrent translocation 6;9 [t(6;9)] leading to DEK::NUP214 fusion, and the other one presenting with concurrent inversion 16 -inv(16)- leading to CBFB::MYH11 fusion. The t(6;9) is usually associated with poor prognosis in acute myeloid leukemia (AML) patients. In this case, the patient failed to achieve remission and expired. This suggests that the t(6;9) is also associated with poor prognosis in CML. However, more data is needed to verify this association. Detection of inv(16) by karyotyping is technically challenging. In addition, FISH for CBFB is not usually run in the context of CML, thus raising the possibility that similar cases may have been underdiagnosed. With the routine use of next-generation sequencing (NGS) for gene fusion detection, more patients like this one should be diagnosed and treated accordingly. These cases illustrate the importance of a comprehensive molecular/cytogenetic diagnostic work-up.
A novel fumarate hydratase frameshift mutation in lung adenocarcinoma: A case report.
Nakagawa H, Aoyama S, Yokobori J … +7 more , Furusawa H, Mitsumura T, Takemoto A, Yamagiwa K, Kawanishi M, Miyazaki Y, Ikeda S
Cancer Genet · 2025 Nov · PMID 40840015 · Publisher ↗
Fumarate hydratase (FH) is a tumor suppressor gene implicated in the tumorigenesis of several cancers, including renal cell carcinoma. However, FH mutations are uncommon in lung adenocarcinoma, and frameshift deletions a...
Fumarate hydratase (FH) is a tumor suppressor gene implicated in the tumorigenesis of several cancers, including renal cell carcinoma. However, FH mutations are uncommon in lung adenocarcinoma, and frameshift deletions are exceedingly rare. Here, we report a novel FH 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 FH 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. FH alterations, such as the one described, could represent potential therapeutic targets from molecular perspectives.
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