Aberrant methylation of tumor suppressor genes and allelic imbalance in cervical intraepithelial neoplasia

Кекеева, Т. В.; Zhevlova, A. I.; Podistov, Yu. I.; Solov’eva, Yu. V.; Zaletaev, D. V.; Немцова, М. В.

doi:10.1134/s0026893306020038

Cited by 11 publications

(9 citation statements)

References 20 publications

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“…Similarly, the TUSC gene encodes a protein with oligosaccahryl transferase activity which was originally identified as a homozygous deletion in metastatic prostate cancer [ 42 ]. TUSC3 has since been shown to be hypermethylated in acute lymphoblastoid leukemia (ALL) cells [ 55 ], as well as in cervical intraepitelial neoplasia [ 56 ], and to be specifically associated with loss of heterozygosity (LOH) on chromosomal band 8p22, a common event in several epithelial tumors including ovarian carcinoma [ 41 ]. Significantly lower expression of TUSC3 was correlated with an increase in clinical grade severity in a study of 58 primary ovarian carcinoma tissues [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

et al. 2008

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Background: The regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. In order to characterize the effect of PKA type I and type II regulatory subunits on gene transcription at a global level, the PKA regulatory subunit genes for RIα and RIIβ were stably transfected into cells of the ovarian cancer cell line (OVCAR8).

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Section: Discussionmentioning

confidence: 99%

Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

et al. 2008

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“…Similarly, the functional relevance of RBSP3 protein in phosphorylation of RB1 along with its localization during tumor progression has not yet been studied. On the other hand, infrequent deletion and promoter hypermethylation of RB1 have been reported in both premalignant and malignant lesions of cervix (Kim et al, 1997;Narayan et al, 2003;Kekeeva et al, 2006). However, association of RBSP3 and RB1 with CACX development has not yet been studied.…”

Section: Introductionmentioning

confidence: 95%

RBSP3 is frequently altered in premalignant cervical lesions: Clinical and prognostic significance

Mitra

Indra

Bhattacharya

et al. 2009

Genes Chromosomes & Cancer

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To understand the importance of frequent deletion of 3p22.3 in cervical carcinogenesis, alterations (deletion/methylation/expression) of the candidate genes STAC, MLH1, ITGA9, and RBSP3, located in the region, were analyzed in 24 cervical intraepithelial neoplasia (CIN) and 137 uterine cervical carcinoma (CACX) samples. In CIN, RBSP3 deletion (48%) and methylation (26%) were high compared with the other genes (4-9%). In CACX, alterations of these genes were as follows: deletion: STAC (54%) > MLH1 (46%) > RBSP3 (45%) > ITGA9 (41%), methylation: RBSP3 (25%) > ITGA9 (24%) > STAC (19%) > MLH1 (13%). Overall, alterations of RBSP3 showed association with CIN, whereas for STAC and MLH1, this frequency increased significantly from CIN --> Stage I/II and for ITGA9 from CIN --> Stage I/II and also from Stage I/II --> Stage III/IV. Quantitative mRNA expression analysis showed differential reduced expression of these genes in CACX concordant to their molecular alterations. The more active RBSP3B splice variant was underexpressed in CACX. RB1 was infrequently deleted in CACX. Concordance was seen between (i) inactivation of RBSP3 and intense p-RB1 nuclear immunostaining and (ii) low/absence of MLH1 expression and its molecular alterations in CACX. In normal cervical epithelium, p-RB1 immunostaining was low in differentiated cells, whereas MLH1 staining was seen in both nucleus and cytoplasm irrespective of differentiation stage. Alterations of the genes were significantly associated with poor prognosis. High parity (>or=5)/early sexual debut (

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“…The ORs were 4.56 (95% CI: 2.62–7.95, P < 0.05) in the MSP group under random effects model, and 4.60 (95% CI: 1.78–11.85, P < 0.05) in the non-MSP group under the fixed-effects model. With regard to the control source, one study 20 had both autologous and heterogeneous samples as control and was divided into two studies. Three studies were excluded since they included blood sample as controls.…”

Section: Resultsmentioning

confidence: 99%

“…About 8 of 29 included studies presented significant association between hypermethylation of MGMT promoter and risk of breast and gynecological cancers in women 16 , 18 , 21 , 23 , 28 , 29 , 31 , 32 , whereas all of the remaining suggested no significant relationship 12 – 17 , 19 , 20 , 22 , 24 – 27 , 30 , 33 – 39 . When all studies were pooled into the meta-analysis, cancer risk associated with MGMT promoter hypermethylation was significant in breast and gynecological cancers.…”

Section: Discussionmentioning

confidence: 99%

Association between MGMT Promoter Methylation and Risk of Breast and Gynecologic Cancers: A Systematic Review and Meta-Analysis

Chen

Zheng

Zhuo

et al. 2017

Sci Rep

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The role of the promoter methylation of O 6-methylguanine-DNA methyltransferase (MGMT) remains controversial for breast and gynecologic cancers. We conducted a meta-analysis to assess the association between hypermethylation of MGMT promoter and the risk of breast and gynecologic cancers. A comprehensive search was conducted in PubMed and Embase electronic databases up to 19th August 2017 for studies about the association between MGMT promoter hypermethylation and breast and gynecologic cancers. A total of 28 articles including 2,171 tumor tissues and 1,191 controls were involved in the meta-analysis. The pooled results showed that MGMT promoter methylation status was significantly associated with an increased risk of breast and gynecologic cancers (OR = 4.37, 95% CI: 2.68–7.13, P < 0.05). The associations were robust in subgroup analysis based on ethnicity, cancer type, methylation detection method, and control source. This meta-analysis indicated that MGMT hypermethylation was significantly associated with the risk of breast and gynecological cancers, and it may be utilized as a valuable biomarker in early diagnostics and prognostication of these cancers. Further efforts are needed to identify and validate this finding in prospective studies, especially in situation with new methylation testing methods and samples from plasma circulating DNA.

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Aberrant methylation of tumor suppressor genes and allelic imbalance in cervical intraepithelial neoplasia

Cited by 11 publications

References 20 publications

Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells

RBSP3 is frequently altered in premalignant cervical lesions: Clinical and prognostic significance

Association between MGMT Promoter Methylation and Risk of Breast and Gynecologic Cancers: A Systematic Review and Meta-Analysis

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