Structural Chromosome Instability: Types, Origins, Consequences, and Therapeutic Opportunities

Siri, Sebastián Omar; Martino, Julieta; Gottifredi, Vanesa

doi:10.3390/cancers13123056

Cited by 38 publications

(28 citation statements)

References 176 publications

(215 reference statements)

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“…The results of our analysis suggest that whole genome doubling is typically accompanied by W-CIN, but not S-CIN. Instead, we find that high SCS is linked to homologous recombination deficiency, highlighting the different processes involved in these two different CIN phenotypes [6].…”

Section: Discussionmentioning

confidence: 55%

“…Although W-CIN can induce S-CIN and vice versa, both types of CIN arise through distinct molecular characteristics. Whilst W-CIN is caused by chromosome missegregation during mitosis, S-CIN is commonly attributed to errors in the repair of DNA double-strand breaks [5,6]. Both types of CIN are intimately related to DNA replication stress [7,8], which not only induces CIN [9,10], but also occurs as an immediate short-term response to aneuploidy and CIN [11].…”

Section: Introductionmentioning

confidence: 99%

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Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types

Zhang

Kschischo

2022

Cancers

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A large proportion of tumours is characterised by numerical or structural chromosomal instability (CIN), defined as an increased rate of gaining or losing whole chromosomes (W-CIN) or of accumulating structural aberrations (S-CIN). Both W-CIN and S-CIN are associated with tumourigenesis, cancer progression, treatment resistance and clinical outcome. Although W-CIN and S-CIN can co-occur, they are initiated by different molecular events. By analysing tumour genomic data from 33 cancer types, we show that the majority of tumours with high levels of W-CIN underwent whole genome doubling, whereas S-CIN levels are strongly associated with homologous recombination deficiency. Both CIN phenotypes are prognostic in several cancer types. Most drugs are less efficient in high-CIN cell lines, but we also report compounds and drugs which should be investigated as targets for W-CIN or S-CIN. By analysing associations between CIN and bio-molecular entities with pathway and gene expression levels, we complement gene signatures of CIN and report that the drug resistance gene CKS1B is strongly associated with S-CIN. Finally, we propose a potential copy number-dependent mechanism to activate the PI3K pathway in high-S-CIN tumours.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types

Zhang

Kschischo

2022

Cancers

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“…Besides small-scale genetic changes, genomic instability includes large-scale genomic events [ 87 ], such as chromosomal instability [ 88 ], aneuploidy, chromothripsis [ 89 ], and extrachromosomal DNA (ecDNA) [ 90 ], that involve an ample number of genes and provide massive copy-number amplification. Large-scale DNA alterations are quite unstable through mitoses and can undergo strong selective pressures, accelerating tumor evolution [ 19 ].…”

Section: Determinants Of Ithmentioning

confidence: 99%

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

Servidei

Lucchetti

Navarra

et al. 2021

Cancers

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Intra-tumoral heterogeneity (ITH) is a complex multifaceted phenomenon that posits major challenges for the clinical management of cancer patients. Genetic, epigenetic, and microenvironmental factors are concurrent drivers of diversity among the distinct populations of cancer cells. ITH may also be installed by cancer stem cells (CSCs), that foster unidirectional hierarchy of cellular phenotypes or, alternatively, shift dynamically between distinct cellular states. Ependymoma (EPN), a molecularly heterogeneous group of tumors, shows a specific spatiotemporal distribution that suggests a link between ependymomagenesis and alterations of the biological processes involved in embryonic brain development. In children, EPN most often arises intra-cranially and is associated with an adverse outcome. Emerging evidence shows that EPN displays large intra-patient heterogeneity. In this review, after touching on EPN inter-tumoral heterogeneity, we focus on the sources of ITH in pediatric intra-cranial EPN in the framework of the CSC paradigm. We also examine how single-cell technology has shed new light on the complexity and developmental origins of EPN and the potential impact that this understanding may have on the therapeutic strategies against this deadly pediatric malignancy.

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“…Intelligent medical imaging uses artificial intelligence technology to analyze and process the scanned images of commonly used medical imaging technologies such as X-ray, CT, magnetic resonance imaging (MRI), and ultrasound and provide diagnostic assistance and prompts [ 17 ]. Based on this, 104 patients with CAHD who underwent coronary angiography (CAG) and PCI surgery after the enhanced coronary CT (ECCT) were treated as the research objects.…”

Section: Introductionmentioning

confidence: 99%

Artificial Intelligence Algorithm‐Based Computed Tomography Image in Assessment of Acute Renal Insufficiency of Patients Undergoing Percutaneous Coronary Intervention

Zhang

Liu

Tian

2022

Contrast Media & Molecular Imaging

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This study was aimed to analyze the changes in renal function of patients undergoing percutaneous coronary intervention (PCI) surgery and the characteristics of their computed tomography (CT) image based on artificial intelligence algorithms. In this study, 104 patients with coronary atherosclerotic heart disease (CAHD) were treated as the research objects. They were divided into an experimental group (patients who underwent CAG and PCI within 1 week after enhanced coronary CT (ECCT)) and the control group (patients who underwent CAG and PCI within 1–3 weeks after ECCT). Renal imaging scans of patients were performed by CT based on discrete inseparable shear transform (DNST) optimized algorithm, which was named as O-DNST. The results showed that the serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein (UP) levels of patients in the experimental group were significantly higher than those of the control group 24–72 hours after surgery, while the levels of endogenous creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) were significantly lower than those of the control group ( P < 0.05). The levels of β2 microglobulin (β2-MG), C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor (TNF-α) in the experimental group were significantly higher than those in the control group 24–72 hours after surgery ( P < 0.05). The incidence of contrast-induced nephropathy (CIN) in the experimental group (15.38%) was significantly higher than that in the control group (5.8%), and the difference was statistically significant ( P < 0.05). The results showed that repeated application of contrast agent in a short period of time can promote the increase of serum inflammation levels in PCI patients, which may be a risk factor for CIN in PCI patients.

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Structural Chromosome Instability: Types, Origins, Consequences, and Therapeutic Opportunities

Cited by 38 publications

References 176 publications

Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types

Distinct and Common Features of Numerical and Structural Chromosomal Instability across Different Cancer Types

Cell-of-Origin and Genetic, Epigenetic, and Microenvironmental Factors Contribute to the Intra-Tumoral Heterogeneity of Pediatric Intracranial Ependymoma

Artificial Intelligence Algorithm‐Based Computed Tomography Image in Assessment of Acute Renal Insufficiency of Patients Undergoing Percutaneous Coronary Intervention

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