Cited by KIF18A in HCC Metastasis: Dual Role in Anoikis Resistance and Chromosome Instability

The Role of Chronic Inflammation in Pediatric Cancer DOI

Christine Mella,

Panogiotis Tsarouhas,

Maximillian Brockwell

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 154

Published: Jan. 6, 2025

Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result tissue fibrosis genetic alterations that contribute to pathogenesis of human diseases such as cancer. Recent scientific advancements exploring underlying mechanisms malignant cellular transformations cancer progression have exposed significant disparities between pediatric adult-onset cancers. For instance, cancers tend lower mutational burdens arise actively developing tissues, where cell-cycle dysregulation leads gene, chromosomal, fusion gene development not seen counterparts. As such, findings adult cannot be directly applied cancers, unique mutations inherent etiologies remain poorly understood. Here, we review processes chromosomal instability, tumor microenvironment, tumorigenesis transformation explore current therapeutic interventions maintain and/or restore inflammatory homeostasis.

Language: Английский

Citations

Transcription Machinery Anchors ecDNAs to Mitotic Chromosomes for Segregation DOI

Ying Xie, Jun Yi Stanley Lim, Wenyue Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Extrachromosomal DNA (ecDNA) is a prevalent driver of cancer, whose random segregation promotes aggressive tumors. Acentric ecDNAs attach to chromosomes during mitosis for segregation. However, the molecular mechanism governing ecDNA-chromosome mitotic interactions remains poorly understood. This study shows that histone 3 lysine 27 acetylation (H3K27ac)-marked chromatin mitosis. H3K27ac depletion resulted in ecDNA detachment from chromosomes. Diverse bromodomain proteins, which are known readers H3K27ac, stabilize ecDNAs’ interaction, exhibiting context-dependent and mutually complementary roles. Furthermore, disruptions Mediator complex RNA polymerase II transcription activity both dissociate chromosomes, suggesting machinery mediates Mis-segregated were expelled into cytosol degraded, leading diminished oncogene expression reversal therapy resistance. Our research provides new insights interplay between acentric inheritance offering novel avenue disrupting ecDNA-driven oncogenesis.

Language: Английский

Citations

Pathological Modulation of Genome Maintenance by Cancer/Testes Antigens (CTAs) DOI

Cyrus Vaziri, Karly Forker, Xingyuan Zhang

et al.

DNA repair, Journal Year: 2025, Volume and Issue: 147, P. 103818 - 103818

Published: Feb. 16, 2025

Language: Английский

Citations

Micronuclei formation: small nuclear packages with big genomic consequences DOI

Andrew Omachoko Onoja, Christopher Didigwu Nwani, Chibuisi G. Alimba

et al.

The Nucleus, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Language: Английский

Citations

Robust assessment of HRD genomic instability by OncoScan microarrays DOI

Ariadna Lara Gutiérrez,

Iris Halbwedl,

Stefan Sauer

et al.

Journal of Molecular Diagnostics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Genomic instability scars are markers for detecting homologous recombination deficiency status in ovarian cancer patients and predicting the response to PARP inhibitor treatment. Currently, only a few reliable validated assays available, with Myriad myChoice CDx being most commonly used commercial assay genomic scar score determination; given need more straightforward, accessible, method methods. In this work we describe feasibility of using microarray OncoScan CNV open-source software packages quantify scores, development an open-access online platform calculation. Our laboratory-developed test accurately classified recombination-proficient recombination-deficient samples based on scores derived from Oncoscan assay. Internally evaluated demonstrated 92% overall agreement higher sample success rate compared externally analyzed scores. The availability HRD determination has doubled number eligible therapy. can be conveniently performed individual samples, facilitates without specialized bioinformatics support.

Language: Английский

Citations

Exploring the Molecular Pathways of Advanced Rectal Cancer: A Focus on Genetic, RNA, and Biological Technique DOI

Ameeduzzafar Zafar,

Mohammad Khalid, Omar Awad Alsaidan

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155956 - 155956

Published: April 1, 2025

Language: Английский

Citations

Establishing genome sequencing and assembly for non-model and emerging model organisms: a brief guide DOI

Tilman Schell, Carola Greve, Lars Podsiadłowski

et al.

Frontiers in Zoology, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 17, 2025

Abstract Reference genome assemblies are the basis for comprehensive genomic analyses and comparisons. Due to declining sequencing costs growing computational power, projects now feasible in smaller labs. De novo non-model or emerging model organisms requires knowledge about size techniques extracting high molecular weight DNA. Next quality, amount of DNA obtained from single individuals is crucial, especially, when dealing with small organisms. While long-read technologies methods choice creating quality assemblies, pure short-read might bear most coding parts a but usually much more fragmented do not well resolve repeat elements structural variants. Several initiatives produce organism genomes provide rules standards assembly. However, sometimes part such an initiative does meet its standards. Therefore, if scientific question can be answered low contiguity intergenic parts, missing chromosome scale assembly should prevent publication. This review describes how set up animal project lab, estimate resources, deal suboptimal conditions. Thus, we aim suggest optimal strategies that fulfil needs according specific research questions, e.g. “How species related each other based on whole genomes?” (phylogenomics), populations within differ?” (population genomics), “Are differences between relevant conservation?” (conservation “Which selection pressure acting certain genes?” (identification genes under selection), “Did repeats expand contract recently?” (repeat dynamics).

Language: Английский

Citations

Tumor associated chromosomal instability drives colorectal adenoma to adenocarcinoma progression based on 17 year follow up evidence DOI

Hui Li, Fang� Yang, Bingjun Bai

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 21, 2025

Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally. Adenomas, precursors to CRC, can be diagnosed early, but the genetic events adenoma-adenocarcinoma conversion remain unclear. This study explored role chromosomal instabilities (CINs) in this conversion. Over 17-year follow-up period, 119 adenomas were analyzed using low-coverage whole-genome sequencing (LC-WGS) and Ultrasensitive Chromosomal Aneuploidy Detector. Risk factors for adenocarcinoma development identified through logistic regression analysis, survival was assessed Kaplan-Meier curves. CIN found 32% adenomas, with higher incidence high-grade (P = 0.0359). Common changes included loss 18q, 1p, 17p gain 8q (MYC), 20q, 7p (EGFR). During follow-up, 88 patients experienced recurrence, including 40 cases 48 progression adenocarcinoma. 40% cases, 33.6% adenoma recurrence 26% nonrecurrent cases. A strong linkage observed before after tumor transformation, high match between tumors matched prior adenomas. significantly associated disease (HR: 2.5, 95% CI: 1.4-4.5, P 0.00162) an independent risk factor. Additionally, MFN2 gene copy number deletion linked and/or resection, reduced expression tissues. In conclusion, key factor progression, adverse outcomes, providing insights more accurate clinical prognostication adenoma-to-adenocarcinoma transformation.

Language: Английский

Citations

Origins of de novo chromosome rearrangements unveiled by coupled imaging and genomics DOI

Marco Raffaele Cosenza, Alice Gaiatto,

Büşra Erarslan Uysal

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract Chromosomal instability results in widespread structural and numerical chromosomal abnormalities (CAs) during cancer evolution 1–3 . While CAs have been linked to mitotic errors resulting the emergence of nuclear atypias 4–7 , underlying processes basal rates spontaneous CA formation human cells remain under-explored. Here we introduce machine learning-assisted genomics-and-imaging convergence (MAGIC), an autonomously operated platform that integrates automated live-cell imaging micronucleated cells, learning real-time, single-cell genomics investigate de novo at scale. Applying MAGIC near-diploid, non-transformed cell lines, track events over successive cycles, highlighting common role dicentric chromosomes as initiating event. We determine baseline rate, which approximately doubles TP53 -deficient show chromosome losses arise more rapidly than gains. The targeted induction DNA double-strand breaks along triggers distinct processes, revealing stable isochromosomes, amplification coordinated segregation isoacentric segments multiples two, complex outcomes, depending on break location. Our data contrast spectra from somatic mutational landscapes after selection occurred. large-scale experimentation enabled by provides insights into formation, paving way unravel fundamental determinants instability.

Language: Английский

Citations

Chromosomal instability as an architect of the cancer stemness landscape DOI

Shahnawaz Ahmad Baba,

Aran Zakeri,

Jay S. Desgrosellier

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 13, 2024

Despite a critical role for tumor-initiating cancer stem cells (CSCs) in breast progression, major questions remain about the properties and signaling pathways essential their function. Recent discoveries highlighting mechanisms of CSC-resistance to stress caused by chromosomal instability (CIN) may provide valuable new insight into underlying forces driving stemness properties. While tolerance is well-known attribute CSCs, CIN-induced distinctive since levels appear increase during tumor initiation metastasis. These dynamic changes CIN serve as barrier constraining effects non-CSCs shaping landscape early stages disease progression. In contrast most other stresses, can also paradoxically activate pro-tumorigenic antiviral signaling. Though seemingly contradictory, this indicate that inflammatory closely collaborate define CSC state. Together, these unique features form basis relationship between

Language: Английский

Citations