Chromosome Abnormalities: New Insights into Their Clinical Significance in Cancer

Kou, Fan; Wu, Lei; Ren, Xiubao; Yang, Lili

doi:10.1016/j.omto.2020.05.010

Cited by 48 publications

(30 citation statements)

References 97 publications

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“…The p-arm of chromosome 3 has dense interactions hotspots in both intra- and inter-trend genes. There is a common deletion in Chr3p in lung cancer (Lerman et al, 2000 ; Kou et al, 2020 ). It is known that several tumor suppressor genes are located at 3p (Varella-Garcia, 2010 ).…”

Section: Resultsmentioning

confidence: 99%

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Loss of Long Distance Co-Expression in Lung Cancer

et al. 2021

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Lung cancer is one of the deadliest, most aggressive cancers. Abrupt changes in gene expression represent an important challenge to understand and fight the disease. Gene co-expression networks (GCNs) have been widely used to study the genomic regulatory landscape of human cancer. Here, based on 1,143 RNA-Seq experiments from the TCGA collaboration, we constructed GCN for the most common types of lung tumors: adenocarcinoma (TAD) and squamous cells (TSCs) as well as their respective control networks (NAD and NSC). We compared the number of intra-chromosome (cis-) and inter-chromosome (trans-) co-expression interactions in normal and cancer GCNs. We compared the number of shared interactions between TAD and TSC, as well as in NAD and NSC, to observe which phenotypes were more alike. By means of an over-representation analysis, we associated network topology features with biological functions. We found that TAD and TSC present mostly cis- small disconnected components, whereas in control GCNs, both types have a giant trans- component. In both cancer networks, we observed cis- components in which genes not only belong to the same chromosome but to the same cytoband or to neighboring cytobands. This supports the hypothesis that in lung cancer, gene co-expression is constrained to small neighboring regions. Despite this loss of distant co-expression observed in TAD and TSC, there are some remaining trans- clusters. These clusters seem to play relevant roles in the carcinogenic processes. For instance, some clusters in TAD and TSC are associated with the immune system, response to virus, or control of gene expression. Additionally, other non-enriched trans- clusters are composed of one gene and several associated pseudo-genes, as in the case of the FTH1 gene. The appearance of those common trans- clusters reflects that the gene co-expression program in lung cancer conserves some aspects for cell maintenance. Unexpectedly, 0.48% of the edges are shared between control networks; conversely, 35% is shared between lung cancer GCNs, a 73-fold larger intersection. This suggests that in lung cancer a process of de-differentiation may be occurring. To further investigate the implications of the loss of distant co-expression, it will become necessary to broaden the investigation with other omic-based approaches. However, the present approach provides a basis for future work toward an integrative perspective of abnormal transcriptional regulatory programs in lung cancer.

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Section: Resultsmentioning

confidence: 99%

“…It is known that several tumor suppressor genes are located at 3p (Varella-Garcia, 2010 ). Partial deletion of 3p occurs in almost all lung carcinomas (Kou et al, 2020 ). This deletion includes tumor suppressor genes, such as RASSF1 (3p21.3) or TUSC2 (FUS1, 3p21.3) (Kok et al, 1997 ).…”

Section: Resultsmentioning

confidence: 99%

Loss of Long Distance Co-Expression in Lung Cancer

et al. 2021

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“…Centrosome amplification is an early event in tumorigenesis, has a strong correlation with CIN and is associated with disease progression and poor prognosis [56]. Aneuploidy, observed in 90% of solid human tumors, correlates with metastatic behavior, drug resistance and poor patient outcome [25,57,58]. CIN, the major cause of aneuploidy, drives tumor heterogeneity, thus promoting recurrence, metastasis and resistance to therapy [26,59].…”

Section: Discussionmentioning

confidence: 99%

“…Chromosome instability (CIN) is the main form of genomic instability leading cells to acquire modifications in chromosomes' structure, such as deletions, inversions and translocations, and numbers [24]. CIN is observed in the vast majority of solid tumors with nearly 90% of human cancers showing aneuploidy and other chromosomal abnormalities [25]. Such instability is an early phenomenon during tumorigenesis and is associated with poor prognosis and multidrug resistance [26].…”

Section: Introductionmentioning

confidence: 99%

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number

Tenan

Nicolle

Moralli

et al. 2021

IJMS

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Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum—in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues—incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

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“…Recently, the predictive potential of SCNAs has been validated in immunotherapy. For example, in patients with NSCLC treated with anti-programmed cell death (ligand) 1 [PD-(L)1] therapy, SCNAs are lower in patients with durable clinical benefit than in those with nondurable benefit; among patients with melanoma treated with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), those with low SCNA experience longer survival than those with high SCNA 12 . SCNAs are a prognostic factor for prostate cancer-specific death 9 .…”

Section: Introductionmentioning

confidence: 99%

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

Kou

Guo

et al. 2021

Cancer Biol Med

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Objective: Lung cancer is the most common cause of cancer-related deaths worldwide. Somatic copy number alterations (SCNAs) have been used to predict responses to therapies in many cancers, including lung cancer. However, little is known about whether they are predictive of radiotherapy outcomes. We aimed to understand the prognostic value and biological functions of SCNAs. Methods: We analyzed the correlation between SCNAs and clinical outcomes in The Cancer Genome Atlas data for 486 patients with non-small cell lung cancer who received radiotherapy. Gene set enrichment analyses were performed to investigate the potential mechanisms underlying the roles of SCNAs in the radiotherapy response. Our results were validated in 20 patients with lung adenocarcinoma (LUAD) receiving radiotherapy. Results: SCNAs were a better predictor of progression-free survival (PFS) in LUAD (P = 0.024) than in lung squamous carcinoma (P = 0.18) in patients treated with radiotherapy. Univariate and multivariate regression analyses revealed the superiority of SCNAs in predicting PFS in patients with LUAD. Patients with stage I cancer and low SCNA levels had longer PFS than those with high SCNA levels (P = 0.022). Our prognostic nomogram also showed that combining SCNAs and tumor/node/metastasis provided a better model for predicting long-term PFS. Additionally, high SCNA may activate the cell cycle pathway and induce tumorigenesis. Conclusions: SCNAs may be used to predict PFS in patients with early-stage LUAD with radiotherapy, in combination with TNM, with the aim of predicting long-term PFS. Therefore, SCNAs are a novel predictive biomarker for radiotherapy in patients with LUAD.

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Chromosome Abnormalities: New Insights into Their Clinical Significance in Cancer

Abstract: Numerical Chromosome Abnormalities AneuploidyAneuploidy, defined as the gain or loss of chromatid or chromosome regions, is a hallmark of cancer. 1 According to different formation mechanisms, aneuploidy is divided into whole

Cited by 48 publications

References 97 publications

Loss of Long Distance Co-Expression in Lung Cancer

Loss of Long Distance Co-Expression in Lung Cancer

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number

Somatic copy number alterations are predictive of progression-free survival in patients with lung adenocarcinoma undergoing radiotherapy

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