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Aneuploidy is prevalent in cancer and has complicated roles in tumorigenesis. Paradoxically, artificially engineered aneuploidy in normal cells reduces cellular fitness by inducing proteotoxic and genotoxic stresses. A better molecular understanding of the multifaceted roles of aneuploidy in cancer evolution offers promising avenues for future cancer therapies. Here, we discuss the patterns and consequences of aneuploidy in human cancer. We highlight recent efforts to explore aneuploidy as a cancer vulnerability and new interventions that exploit this vulnerability for cancer treatment.
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http://dx.doi.org/10.1016/j.ceb.2025.102490 | DOI Listing |
Mol Oncol
March 2025
Department of Medical Oncology and Cancer Genomics Netherlands, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands.
Cell-free circulating tumor DNA (ctDNA) has emerged as a promising biomarker for response evaluation in metastatic castration-resistant prostate cancer (mCRPC). The current study evaluated the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), a quick, tumor-agnostic and affordable ctDNA assay that requires a small input of DNA, to generate a genome-wide aneuploidy (GWA) score in mCRPC patients, and correlated this to matched metastatic tumor biopsies. In this prospective multicenter study, GWA scores were evaluated from blood samples of 196 mCRPC patients prior to treatment (baseline) with taxanes (docetaxel and cabazitaxel) and androgen receptor signaling inhibitors (ARSI; abiraterone and enzalutamide), and from 74 mCRPC patients at an early timepoint during treatment (early timepoint; median 21 days).
View Article and Find Full Text PDFEcotoxicol Environ Saf
March 2025
Department of Radiobiology and Hygiene Management, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan. Electronic address:
In Japan, several workers were diagnosed with bladder cancer 10-40 years after exposure to 4,4'-methylenebis(2-chloroaniline) (MOCA), mainly through the skin. MOCA also induces bladder cancer in dogs and nonbladder (breast, liver, lung) cancers in rodents. MOCA with S9 fractions contains mutagenic metabolites after catalysis by N-acetyl transferase (NAT).
View Article and Find Full Text PDFBMC Immunol
March 2025
Department of Gastroenterology, Jiangnan University Medical Center, Wuxi No.2 People's Hospital, Wuxi, Jiangsu Province, China.
Background: Hepatocellular carcinoma (HCC) is the most frequent kind of liver cancer with high morbidity and mortality rates worldwide. Altered expression of BUB1 (budding uninhibited by benzimidazole 1) gene leads to chromosome instability and aneuploidy. This study investigated the expression of BUB1 and its prognostic value as well as its correlation with immune cell infiltration and immune checkpoints in HCC.
View Article and Find Full Text PDFJ Cell Mol Med
March 2025
Faculty of Medicine, Division of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland.
We present a case of acute clonal bone marrow 98% infiltration of atypical myeloid cells with borderline hypogranular/agranular promyelocytes/myelocytes and occasional blast cells maturity, which also formed extramedullary tumours in the chest wall, with isolated trisomy of chromosome 6 and pathogenic variant U2AF1 (S34F) that escapes established acute myeloid leukaemia (AML) diagnostic criteria according to the World Health Organization (WHO) classification. Following standard daunorubicin and cytarabine induction therapy, the disease progressed with the appearance of a previously undetected clone of leukaemic cells with a distinct immunophenotype demonstrating monocytoid differentiation and clonal evolution to a hypo-tetraploid karyotype with an average number of 84 chromosomes and new pathogenic NRAS and ZRSR2 mutations. The patient reactivated refractory disseminated intravascular coagulation (DIC) leading to a progressive supratentorial hematoma and finally cardiac arrest.
View Article and Find Full Text PDFSci Rep
March 2025
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Head and neck squamous cell carcinoma (HNSCC) remains a prevalent and lethal malignancy, with a five-year survival rate of just 50% for cases of locally advanced disease. Chromosomal aberrations, particularly the deletion of the short arm of chromosome 3 (3p), have been strongly associated with poor prognosis and more aggressive tumor phenotypes. The tumor microenvironment (TME) plays a pivotal role in tumor progression and resistance to therapy.
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