The Contribution of Genetic and Epigenetic Changes in Granulosa Cell Tumors of Ovarian Origin

Dhillon, Varinderpal S.; Aslam, Mohammad; Husain, Syed Akhtar

doi:10.1158/1078-0432.ccr-04-0228

Cited by 34 publications

(27 citation statements)

References 40 publications

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“…We studied genetic instabilities and promoter methylation status and showed a close association between MSI and promoter hypermethylation. MSI arises through defective DNA mismatch repair genes, which exhibit allelic imbalance in 80% of squamous cell carcinomas of the head and neck (45), and closely associates with gene silencing through promoter hypermethylation (31,33,46). Recent findings indicate that MSI and aberrant promoter hypermethylation selectively but not randomly occurred to specific susceptible sites, resulting in a functional impact on the initiation and progression of tumors (47).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression

Maeda

Chiba

Kawashiri

et al. 2007

Clinical Cancer Research

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Purpose: The loss of epithelial phenotypes in the process of carcinoma progression correlates with clinical outcome, and genetic/epigenetic changes accumulate aggressive clones toward uncurable disease. InB kinase-a (IKKa) has a decisive role in the development of the skin and establishes keratinocyte phenotypes.We assessed clinical implications of IKKa expression in oral carcinomas and epigenetic aberrations for the loss of expression. Experimental Design: We examined IKKa expression in oral carcinomas by immunostaining (n = 64) and genetic instability by microsatellite PCR (n = 46). Promoter methylation status was analyzed by bisulfite-modified sequence (n = 11). Results: IKKa was expressed in the nucleus of basal cells of normal oral epithelium, but not or marginally detected in 32.8% of carcinomas. The immunoreactivity was significantly decreased in less differentiated carcinomas (P < 0.05) and correlated to long-term survival of patients (P < 0.01) with an independent prognostic value (P < 0.05). Although allelic/biallelic loss of the gene was limited to four cases, we detected microsatellite instability in 63.0% cases in which the immunoreactivities were decreased and the promoter was hypermethylated. Conclusion: These results showed that oral carcinomas exhibiting genetic instability and promoter hypermethylation down-regulate expression of IKK and suggest that the epigenetic loss of the expression closely associates with disease progression toward unfavorable prognosis.

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Section: Discussionmentioning

confidence: 99%

Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression

Maeda

Chiba

Kawashiri

et al. 2007

Clinical Cancer Research

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“…INK4a methylation in ovarian cancer tissues have ranged from 0% to 40% (21,23,32,33). One study indicated that methylation of p16…”

Section: Discussionmentioning

confidence: 99%

Methylation and Messenger RNA Expression of p15INK4b but Not p16INK4a Are Independent Risk Factors for Ovarian Cancer

Liu¹,

Wang²,

Luo³

et al. 2005

Clinical Cancer Research

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Purpose: The purpose of this research was to compare methylation status and mRNA expression of p15INK4b and p16 INK4a in serous epithelial ovarian cancer tissues and normal ovarian tissues. Experimental Design: We analyzed the DNA methylation status and mRNA expression of p15INK4b and p16 INK4a in 52 ovarian cancer specimens and 40 normal ovarian specimens by using methylation-specific PCR and real-time reverse transcription-PCR, respectively. Results: Although the p15INK4b and p16 INK4a mRNA expression levels were highly correlated with each other (P < 0.001), the methylation status did not seem to be linked with levels of mRNA expression, as no association between the two events was found for either gene. Promoter hypermethylation of p15 INK4b was more common in ovarian cancer (30.8% for the 52 cases) than in normal ovaries (5% for the 40 controls without ovarian cancer; P = 0.005) but not methylation of p16INK4a (25% for cancer versus 37.5% for normal; P = 0.288). The relative mRNA expression levels of p15INK4b were significantly lower in ovarian cancer (12.9%) than in normal ovaries (41.7%; P = 0.008) but not those of p16INK4a (27% for cases versus 32.8% for controls; P = 0.754). Only high methylation rate and low mRNA expression of p15INK4b were independent risk factors for ovarian cancer (adjusted odds ratio, 5.67; 95% confidence interval, 0.85-37.9 for high methylation rate and odds ratio, 8.98; 95% confidence interval, 1.58-50.9 for low mRNA expression, respectively). Conclusions: Our results suggest that epigenetic alterations in p15INK4b but not p16 INK4a have an important role in ovarian carcinogenesis and that mechanisms other than methylation may exist to reduce gene expression of p15INK4b in ovarian cancer.

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“…Since more than 90% of all human cancers are of epithelial origin, MN assay with Buccal epithelial cells is the most suitable biomonitoring approach for the detection of increased cancer risk in humans. Buccal cells have limited DNA repair capacity relative to peripheral blood lymphocytes, and therefore, may more accurately reflect age-related genomic instability event in epithelial tissue (Dhillon et al, 2004). A significant increase in the frequencies of MN was observed in exfoliated Buccal cells of polycystic ovarian syndrome patients (Nersesyan and Chobanyan, 2010).…”

Section: Discussionmentioning

confidence: 99%

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome

Sekar¹,

Nair²,

Francis³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value (45.9°) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

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The Contribution of Genetic and Epigenetic Changes in Granulosa Cell Tumors of Ovarian Origin

Cited by 34 publications

References 40 publications

Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression

Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression

Methylation and Messenger RNA Expression of p15INK4b but Not p16INK4a Are Independent Risk Factors for Ovarian Cancer

Multi-Parameter Approach for Evaluation of Genomic Instability in the Polycystic Ovary Syndrome

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