Aberrant chromatin remodeling in gynecological cancer (Review)

Okawa, Ryuichiro; Banno, Kouji; Iida, Miho; Yanokura, Megumi; Takeda, Takashi; Iijima, Moito; Kunitomi-Irie, Haruko; Nakamura, Kenzo; Adachi, Manabu; Umene, Kiyoko; Nogami, Yuya; Masuda, Kenta; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

doi:10.3892/ol.2017.6891

Cited by 8 publications

(10 citation statements)

References 63 publications

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“…1 illustrates the effects of the loss of ARID1A expression and its impact on carcinogenesis, although the precise mechanisms that triggers cancer development have not yet been fully elucidated. ARID1A expression disorders disrupt the function of SWI/SNF and the chromatin remodeling mechanism, causing epigenetic abnormalities in gene expression with severe consequent effects in the cell identity and possible carcinogenicity (41,(84)(85)(86). In addition, functional studies of ARID1A have demonstrated that its tumour-suppressive action lies both in the control of cellular proliferation and in maintaining the integrity of the genetic material, which is why both roles of guardian and caretaker of the genome are attributed to it (3,13).…”

Section: Abnormal Epigenetic Regulation Of Arid1a Expressionmentioning

confidence: 99%

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Pavlidou

Balis

2020

World Acad Sci J

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Mutations of the ARID1A gene, which encodes the basic directional subunit of SWI/SNF chromatin remodeling complexes, were detected in the middle of the last decade in several cancerous tissue types, highlighting its tumour-suppressive role. Since then, functional studies of the homologous protein have indicated that through its interactions with nucleosomal DNA, transcription factors and nuclear hormone receptors, it plays a key role in regulating cellular proliferation, gene expression and the repair of genetic material, while the loss of its expression triggers carcinogenesis, through mechanisms which have not yet been elucidated. This bibliographic review of clinical investigations focused on the detection of ARID1A mutations and expression levels in malignant tumours, as well as on their association with the prognosis of ARID1A-deficient patients exhibiting a high degree of heterogeneity in the corresponding research findings. The clarification of the prognostic significance of the gene requires further investigation, focusing on cancers and patients of common clinicopathological features. Contents1. Introduction 2. Summary of the materials and methods used for analysis in previous studies 3. Summary of the findings of previous studies regarding ARID1A in cancer 4. Discussion 5. Conclusion and future therapeutic perspectives

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Section: Abnormal Epigenetic Regulation Of Arid1a Expressionmentioning

confidence: 99%

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Pavlidou

Balis

2020

World Acad Sci J

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“…In addition, somatic mutations private to either the SBT or HGSC were identified; the SBT harboured a CDKN2A hotspot mutation, and the HGSC showed SMARCA4 and CREBBP loss‐of‐function mutations coupled with LOH, as well as EP300 and MYCL1 missense mutations (Figure ). Of note, SETD2 , EP300 and SMARCA4 are chromatin‐remodelling genes, aberrations in which play an important role in carcinogenesis . These data suggest that, although the SBT and HGSC of case 2 are clonally related, parallel evolution took place and the lesions acquired private driver alterations.…”

Section: Resultsmentioning

confidence: 88%

“…Ovarian tumours that commonly show alterations in chromatin‐remodelling genes include clear cell and endometrioid carcinomas, and small cell carcinomas of hypercalcaemic type . Alterations in several genes involved in chromatin remodelling have also been reported in serous carcinomas, more commonly in those arising in the endometrium (including CHD4 , EP300 , ARID1A , FBXW7 , and SPOP ) than in those arising in the adnexa . The Cancer Genome Atlas (TCGA) analyses identified SMARCA4 alterations in a minority of ovarian HGSCs, a small subset of which lacked identifiable TP53 mutations .…”

Section: Discussionmentioning

confidence: 99%

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Somatic genetic alterations in synchronous and metachronous low‐grade serous tumours and high‐grade carcinomas of the adnexa

et al. 2019

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Aims Low‐grade serous carcinomas (LGSCs) and their precursors serous borderline tumours (SBTs) characteristically harbour mutations in BRAF, KRAS or NRAS but rarely in TP53, whereas high‐grade serous carcinomas (HGSCs) are characterised by frequent TP53 mutations but rare BRAF, KRAS or NRAS mutations. In a small subset of cases, LGSCs and/or SBTs develop into high‐grade tumours, including HGSCs and poorly differentiated carcinomas (PDCs). Here, we sought to define the repertoire of somatic genetic alterations in low‐grade serous tumours and synchronous or metachronous high‐grade adnexal carcinomas. Methods and results DNA extracted from five SBTs/LGSCs and synchronous or metachronous HGSCs/PDCs and matched normal tissue was subjected to massively parallel sequencing targeting all exons and selected non‐coding regions of 341 cancer‐related genes. The low‐grade and high‐grade tumours from a given case were related, and shared mutations and copy number alterations. Progression from low‐grade to high‐grade lesions was observed, and involved the acquisition of additional mutations and/or copy number alterations, or shifts from subclonal to clonal mutations. Only two (an HGSC and a PDC) of the five high‐grade tumours investigated harboured TP53 mutations, whereas NRAS and KRAS hotspot mutations were seen in two HGSCs and one HGSC, respectively. Conclusions Our results suggest that progression from SBT to HGSC may take place in a subset of cases, and that at least some of the rare HGSCs lacking TP53 mutations may be derived from a low‐grade serous precursor.

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“…The loss of PR expression and functionality in endometrial cancer cells could stimulate MYC the expression of MYC [196]. In addition to an imbalance in the levels of ER/PR signaling and their effector nuclear receptor (NR) coregulators [197], the development of endometrial cancer is also regulated by the DNA repair activity of DNA mismatch repair (MMR) pathways, silencing/ mutations in tumor suppressors, and dysregulation of the chromatin remodeling pathways [198,199,200,201]. In general, a reduction in the level of MMT repair activity combined with growth promoting ER’s genomic- and -nongenomic signaling events might also contribute to growth stimulation.…”

Section: Endometrial Cancermentioning

confidence: 99%

Epigenetic Dysregulation at the Crossroad of Women’s Cancer

Kumar

Paul

Rameshwar

et al. 2019

Cancers

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An increasingly number of women of all age groups are affected by cancer, despite substantial progress in our understanding of cancer pathobiology, the underlying genomic alterations and signaling cascades, and cellular-environmental interactions. Though our understanding of women’s cancer is far more complete than ever before, there is no comprehensive model to explain the reasons behind the increased incidents of certain reproductive cancer among older as well as younger women. It is generally suspected that environmental and life-style factors affecting hormonal and growth control pathways might help account for the rise of women’s cancers in younger age, as well, via epigenetic mechanisms. Epigenetic regulators play an important role in orchestrating an orderly coordination of cellular signals in gene activity in response to upstream signaling and/or epigenetic modifiers present in a dynamic extracellular milieu. Here we will discuss the broad principles of epigenetic regulation of DNA methylation and demethylation, histone acetylation and deacetylation, and RNA methylation in women’s cancers in the context of gene expression, hormonal action, and the EGFR family of cell surface receptor tyrosine kinases. We anticipate that a better understanding of the epigenetics of women’s cancers may provide new regulatory leads and further fuel the development of new epigenetic biomarkers and therapeutic approaches.

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Aberrant chromatin remodeling in gynecological cancer (Review)

Cited by 8 publications

References 63 publications

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Diagnostic significance and prognostic role of the ARID1A gene in cancer outcomes (Review)

Somatic genetic alterations in synchronous and metachronous low‐grade serous tumours and high‐grade carcinomas of the adnexa

Epigenetic Dysregulation at the Crossroad of Women’s Cancer

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