Replication Timing Aberrations and Aneuploidy in Peripheral Blood Lymphocytes of Breast Cancer Patients

Grinberg–Rashi, Helena; Cytron, Shmuel; Gelman-Kohan, Z; Litmanovitch, Talia; Avivi, Lydia

doi:10.1593/neo.10568

Cited by 21 publications

(20 citation statements)

References 37 publications

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“…Surprisingly, the asynchronous replication pattern observed in cancer patients is not restricted to tumor tissue but also occurs in noncancerous cells as well [66,67,68,69,70]. This is best exemplified by the presence of aberrant asynchronous replication between alleles in the peripheral lymphocytes of individuals with solid tumors [66,67].…”

Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

“…Interestingly, this altered replication-timing pattern is present in pre-malignant cells, in individuals pre-disposed to cancer, and in individuals living in polluted areas with a high likelihood of getting cancer, suggesting that this may be an early event during carcinogenesis [63,65,67,72]. The replication asynchrony observed in cancerous tissue and normal cells in individuals with cancer is generally a result of the earlier replication of one of the alleles [67,70,72], however, in some cases the delayed replication of one allele has been detected [71]. This aberrant asynchronous replication is heritable (i.e.…”

Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

“…the earlier-replicating allele will be earlier replicating in all subsequent generations) but not dependent on parental origin and therefore resembling the process of human X chromosome inactivation and/or allelic exclusion [73]. Chemotherapy is not sufficient to correct the cancer-associated replication asynchrony detected in lymphocytes of cancer patients [70], but allogeneic stem cell transplantation, in vitro fusion to normal cells, or inhibiting DNA methylation by treating cells with 5-azacytidine can switch replication back to the normal state [69,73,74,75]. …”

Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

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DNA replication timing, genome stability and cancer

Donley

Thayer

2013

Seminars in Cancer Biology

103

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Normal cellular division requires that the genome be faithfully replicated to ensure that unaltered genomic information is passed from one generation to the next. DNA replication initiates from thousands of origins scattered throughout the genome every cell cycle; however, not all origins initiate replication at the same time. A vast amount of work over the years indicates that different origins along each eukaryotic chromosome are activated in early, middle or late S phase. This temporal control of DNA replication is referred to as the replication-timing program. The replication-timing program represents a very stable epigenetic feature of chromosomes. Recent evidence has indicated that the replication-timing program can influence the spatial distribution of mutagenic events such that certain regions of the genome experience increased spontaneous mutagenesis compared to surrounding regions. This influence has helped shape the genomes of humans and other multicellular organisms and can affect the distribution of mutations in somatic cells. It is also becoming clear that the replication-timing program is deregulated in many disease states, including cancer. Aberrant DNA replication timing is associated with changes in gene expression, changes in epigenetic modifications and an increased frequency of structural rearrangements. Furthermore, certain replication timing changes can directly lead to overt genomic instability and may explain unique mutational signatures that are present in cells that have undergone the recently described processes of “chromothripsis” and “kataegis”. In this review, we will discuss how the normal replication timing program, as well as how alterations to this program, can contribute to the evolution of the genomic landscape in normal and cancerous cells.

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Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

Section: Dna Replication Timing and The Evolution Of The Cancer Gementioning

confidence: 99%

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DNA replication timing, genome stability and cancer

Donley

Thayer

2013

Seminars in Cancer Biology

103

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“…Based on Mendelian genetics, mammals receive two alleles of each gene from their parents. Both alleles are regulated symmetrically with respect to expression activity, and replication is synchronous, such as in the case of the genes TP53, RB1, AML1, HER2, and C-MYC (Hiratani and Gilbert, 2009;Grinberg-Rashi et al, 2010). However, monoallelically expressed genes are also found in the genome, in which the replication of the DNA of the two alleles is asynchronous, such as in SNRPN (Hiratani and Gilbert, 2009;Grinberg-Rashi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…A number of studies have shown the known monoallelically expressed genes are nonsynchronous (Hiratani and Gilbert, 2009;Grinberg-Rashi et al, 2010). These genes include the following examples: 1) imprinted genes, particularly the Prader-Willi/Angelman syndrome gene SNRPN; the paternal allele replicates earlier than the maternal allele (Knoll et al, 1994;Gunaratne et al, 1995;Simon et al, 1999); 2) genes on the inactive X chromosome in females (Boggs and Chinault, 1994); and 3) exclusively biallelic genes (Mostoslavsky et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Replication timing regulation in adults with chromosomal balance rearrangements

Xie¹,

Wu²,

Su³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The alternative forms of the alleles in biallelic genes display a synchronous pattern of replication that is different from genes subjected to monoallelic expression, which exhibit an asynchronous mode of replication. The present study sought to gain insight into changes in the allele-specific replication timing in phenotypically normal humans with balanced chromosomal rearrangements, and to investigate the potential mechanism for chromosomal rearrangements. We used fluorescence in situ hybridization and chose biallelic gene expression of RB1 and monoallelic expression of SNRPN in phytohemagglutininstimulated lymphocytes to compare differences in the allelic replication timing. We found that compared to genetically normal adult controls, adults with a normal phenotype despite chromosomal rearrangements showed normal replication timing (synchronous or asynchronous) for the RB1 gene and SNRPN genes. Our data support a link between chromosomal aberrations and epigenetic stability in phenotypically normal humans, independent of the breakpoints in chromosomal structural disruption, and represent an epigenetic mark for allelic exclusion in balanced chromosomal rearrangements in patients with normal phenotypes.

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A new light on DNA replication from the inactive X chromosome

Aladjem

2014

BioEssays

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While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, “silent” chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular.

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Replication Timing Aberrations and Aneuploidy in Peripheral Blood Lymphocytes of Breast Cancer Patients

Abstract: The HER2 and CEN17 aberrant replication differentiated clearly between BCA patients and control subjects. Thus, monitoring the replication of these genes offers potential blood markers for the detection and monitoring of breast cancer.

Cited by 21 publications

References 37 publications

DNA replication timing, genome stability and cancer

DNA replication timing, genome stability and cancer

Replication timing regulation in adults with chromosomal balance rearrangements

A new light on DNA replication from the inactive X chromosome

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