Chromosomal instability: A common feature and a therapeutic target of cancer

Tanaka, Kozo; Hirota, Toru

doi:10.1016/j.bbcan.2016.06.002

Cited by 69 publications

(81 citation statements)

References 180 publications

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“…Notably, these M phase defects were associated with an uncondensed and dispersed chromosome structure, which can trigger chromosomal/genomic instability. Chromosomal instability is a hallmark of cancer cells accompanied with aneuploidy and an abnormal number of chromosomes, mainly caused by chromosome missegregation [106]. Importantly, a number of studies showed that pRB inactivation increased chromosomal instability [25–27, 107].…”

Section: Prb-mediated Regulation Of Higher-order Chromatin Structumentioning

confidence: 99%

Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

Uchida

2016

BioMed Research International

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Retinoblastoma protein (pRB) interacts with E2F and other protein factors to play a pivotal role in regulating the expression of target genes that induce cell cycle arrest, apoptosis, and differentiation. pRB controls the local promoter activity and has the ability to change the structure of nucleosomes and/or chromosomes via histone modification, epigenetic changes, chromatin remodeling, and chromosome organization. Functional inactivation of pRB perturbs these cellular events and causes dysregulated cell growth and chromosome instability, which are hallmarks of cancer cells. The role of pRB in regulation of nucleosome/chromatin structures has been shown to link to tumor suppression. This review focuses on the ability of pRB to control nucleosome/chromatin structures via physical interactions with histone modifiers and chromatin factors and describes cancer therapies based on targeting these protein factors.

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Section: Prb-mediated Regulation Of Higher-order Chromatin Structumentioning

confidence: 99%

Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

Uchida

2016

BioMed Research International

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“…Mitotic defects leading to unequal chromosome segregation are a common cause of chromosomal instability (CIN) and cancer 10 . Defective chromosome segregation and aneuploidy can be caused by dysfunction of the factors regulating proper assembly and dynamics of the mitotic apparatus, sister chromatid cohesion, bipolar attachment of kinetochores to the mitotic spindle and the spindle assembly checkpoint 11 .…”

Section: Introductionmentioning

confidence: 99%

Rescue from replication stress during mitosis

Fragkos

Naim

2017

Cell Cycle

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Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

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“…While, in this review, we focused the attention on structural rearrangements in cancer, it must be emphasized that the large majority of tumors have an aneuploid chromosome set [Thompson and Compton, 2011;McGranahan et al, 2012;Tanaka and Hirota, 2016]. Molecular mechanisms of cancer rearrangements are described in recent and complete reviews [Mertens et al, 2015;Weckselblatt and Rudd, 2015;Willis et al, 2015].…”

Section: Discussionmentioning

confidence: 99%

Chromosome Imbalances in Cancer: Molecular Cytogenetics Meets Genomics

Palumbo

Russo²

2016

Cytogenet Genome Res

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Genomic instability is a hallmark of cancer, and it is well-known that in several cancers the karyotype is unstable and rapidly evolving. Molecular cytogenetics has contributed to the description and interpretation of cancer karyotypes, in particular through multicolor FISH approaches which can define even complex chromosome rearrangements. The introduction of genome-wide methods has made available a powerful set of tools with higher resolution than cytogenetics, thus appropriate to comprehend the huge variability of cancer cells. This review focuses on novel findings deriving from the combination of cytogenetic and genomic approaches in cancer research.

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Chromosomal instability: A common feature and a therapeutic target of cancer

Cited by 69 publications

References 180 publications

Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

Roles of pRB in the Regulation of Nucleosome and Chromatin Structures

Rescue from replication stress during mitosis

Chromosome Imbalances in Cancer: Molecular Cytogenetics Meets Genomics

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