Aneuploidy and malignancy: an unsolved equation

Dey, Pranab

doi:10.1136/jcp.2004.018952

Cited by 62 publications

(58 citation statements)

References 63 publications

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“…The centrosome amplification leads to tumorigenesis through abnormal cell division and resulting chromosome instability. 4,7,36,44,45 Thus, it would be interesting to investigate whether elevated levels of USP1 correlates with increased centrosome abnormalities in human cancers. In summary, we have demonstrated for the first time that Usp1 plays a novel role in regulating centrosome duplication.…”

Section: Discussionmentioning

confidence: 99%

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

2016

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Defects in the regulation of centrosome duplication lead to tumorigenesis through abnormal cell division and resulting chromosome missegregation. Therefore, maintenance of accurate centrosome number is critical for cell fate. The deubiquitinating enzyme USP1 plays important roles in DNA repair and cell differentiation. Importantly, increased levels of USP1 are detected in certain types of human cancer, but little is known about the significance of USP1 overexpression in cancer development. Here we show that Usp1 plays a novel role in regulating centrosome duplication. The ectopic expression of wild-type Usp1, but not C90S Usp1 (catalytically inactive mutant form), induced centrosome amplification. Conversely, ablation of Usp1 in mouse embryonic fibroblasts (MEFs) showed a significant delay in centrosome duplication. Moreover, Usp1-induced centrosome amplification caused abnormal mitotic spindles, chromosome missegregation and aneuploidy. Interestingly, loss of inhibitor of DNA binding protein 1 (ID1) suppressed Usp1-induced centrosome amplification. Taken together, our results strongly suggest that Usp1 is involved in the regulation of centrosome duplication, at least in part via ID1, and Usp1 may exert its oncogenic activity, partially through inducing centrosome abnormality.

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Section: Discussionmentioning

confidence: 99%

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

2016

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“…Chromosomal instability and aneuploidy, the gain and loss of chromosomes, is a characteristic of most malignant cells that is seen during the early stages of tumor development (1,2). It is thought that such alterations lead to the deregulation of the signalling network within the cells with the loss of tumor suppressor genes and the overexpression of oncogenes that drive tumorigenesis (3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

The cohesin-interacting protein, precocious dissociation of sisters 5A/sister chromatid cohesion protein 112, is up-regulated in human astrocytic tumors

et al. 2010

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Abstract. Glioblastoma multiforme (GBM) is the most prevalent, highly malignant, invasive and difficult-to-treat primary brain tumor in adults. At the genetic level, it is characterized by a high degree of chromosomal instability and aneuploidy. It has been shown that defects in the mitotic spindle checkpoint could lead to the development of aneuploidy as well as tumorigenesis. Additional proteins regulating sister chromatid cohesion could also be involved in maintaining the fidelity of chromosome segregation. One such protein is the precocious dissociation of sisters 5A (Pds5A), also known as sister chromatid cohesion protein 112. It is a nuclear protein, expressed from the S right through to the mitotic phase. It is highly conserved from yeast to man and plays a role in the establishment, maintenance and dissolution of sister chromatid cohesion. The mutation of Pds5A orthologs in lower organisms results in chromosome missegregation, aneuploidy and DNA repair defects. It is considered that such defects can cause either cell death or contribute to the development of cancer cells. Indeed, altered expression levels of Pds5A have been observed in tumors of the breast, kidney, oesophagus, stomach, liver and colon. Malignant gliomas, however, have not been analysed so far. Herein, we report on the cloning of Rattus norvegicus Pds5A and on the analysis of its expression pattern in rat tissue. We also show that Pds5A is significantly overexpressed at both the mRNA and protein level and that this overexpression correlates positively with the WHO grade of human gliomas. However, functional assays show that the siRNA-mediated knockdown of Pds5A affects sister chromatid cohesion but does not influence mitotic checkpoint function or the proliferation and survival of GBM cells. Although the mechanism by which Pds5A functions in GBM cells remains unclear, its overexpression in high grade gliomas implies that it could play a pivotal role during the development and progression of astrocytic tumors.

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“…It is a common molecular pathological characteristic in human carcinoma (7,15,16). A number of studies have suggested that using DNA probes for the detection of aneuploidy in cancer cells may be a superior technique to conventional pathological diagnosis (8)(9)(10)(11)(12)14).…”

Section: Discussionmentioning

confidence: 99%

Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

Awut¹,

Niyaz²,

Biekemitoufu³

et al. 2011

Oncology Letters

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Abstract. Chromosome abnormalities in cancer cells occur early in carcinogenesis. We employed DNA probes for the detection of cancer cells in surgical specimens in Kazakh patients with suspected esophageal carcinoma, to analyze the application of this technique during the early diagnosis of esophageal cancer. Comparative analysis was used to compare the results of pathological diagnosis with the results of FISH. We performed esophagofiberscopic biopsy examinations in 50 Kazakh patients with suspected esophageal carcinoma, including 40 males and 10 females, with an average age of 56.8 years. The final diagnosis was esophageal squamous cell carcinoma in 47 patients, and adenocarcinoma, mucinous carcinoma and small cell carcinoma in one patient each. The pathological findings of the biopsy were positive in 45 cases, and false-negative in 5. The sensitivity and specificity of pathological diagnosis were 87.2 and 100%, respectively. Using FISH to examine the same tissues, we found that 48 cases showed aberrant copy numbers in either chromosome 3 or 17, and 2 cases were false-negative, with a sensitivity and specificity of 94.8 and 100%, respectively. The copy numbers of centromeres in chromosome 3 were significantly higher than the copy numbers of centromeres in chromosome 17 (P=0.0001). Compared with biopsy pathology, the FISH test was more sensitive. Being an objective and qualitative method, the technology of molecular pathological diagnosis may effectively increase the early diagnostic rate of esophageal cancer. In addition, the centromere probe in chromosome 3 may be the most sensitive probe for the diagnosis of esophageal cancer in Kazakh patients. IntroductionThe incidence of esophageal cancer (EC) has been high (68.88/100,000) among the Kazakh people living in the Xinjiang Uygur Autonomous Region (Northwest of China) during the past 30 years. Nevertheless, early detection and treatment rates of EC remain low, and it consequently has a poor prognosis. If early diagnosis and treatment were possible, the 5-year survival rate could be increased to above 90% as in other countries/regions that have early detection programs (1-3).Conventional pathological diagnosis plays a crucial role in the diagnosis of EC, and provides important information on tumor differentiation and the degree of morphological changes (4,5). However, due to the limitations of biopsy pathology, discrepancies between pathological diagnosis and actual diagnosis occasionally occur, making clinical diagnosis and treatment difficult. There is, therefore, a need to find a more objective and quantitative method to distinguish benign from malignant cells.A number of studies suggest that the incidence and evolution of EC involves a variety of chromosomal anomalies. During carcinogenesis, a cell goes through molecular cytogenetic changes prior to showing morphological changes. Nuclear chromosome abnormality, which can be observed in cancer cells, is an early event during the process of tumorigenesis, and it has become the determining objective index of c...

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Aneuploidy and malignancy: an unsolved equation

Cited by 62 publications

References 63 publications

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

A novel role for the deubiquitinase USP1 in the control of centrosome duplication

The cohesin-interacting protein, precocious dissociation of sisters 5A/sister chromatid cohesion protein 112, is up-regulated in human astrocytic tumors

Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

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