Methylation Status and Immunohistochemistry of BRCA1 in Epithelial Ovarian Cancer

Pradjatmo, Heru; Dasuki, Djaswadi; Anwar, Mohammad Faiyaz; Miceli, Sofia; Harijadi, .

doi:10.7314/apjcp.2014.15.21.9479

Cited by 13 publications

(12 citation statements)

References 32 publications

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“…However, the occurrence of methylation DOI:http://dx.doi.org/10.7314/APJCP.2015.16.18.8599 Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers was influenced by environtment and nutritional factors as already stated in the literature. Our finding was new evidence for Indonesian people that BRCA genes are highly methylated in ovarian cancer patients, as the previous studied of methylation status for BRCA1 (Pradjatmo et al, 2014). Kontorovich et al (2009) found that BRCA2 does not exhibit a similar methylation profile in ovarian cancer.…”

Section: Brca2 Expression Induced Better Survivalsupporting

confidence: 66%

“…The BRCA2 protein is important to preserve genomic stability by ensuring high fidelity repair of double-strand DNA breaks (McCabe et al, 2006). Previous studies reported BRCA1 methylation in ovarian cancer was 5% (Catteau et al, 1999), 15% (Baldwin et al, 2000), 19% (Hedenfalk et al, 2001), 10% (Rathi et al, 2002), 31% (Meetei et al, 2004), even in our previous study in the Indonesian population found BRCA1 methylation as high as 89.9 % (Pradjatmo et al, 2014). These results support that the abnormal promoter methylation in BRCA1 may have an important role in tumorigenesis in some types of ovarian cancer.…”

Section: Methylation Status and Expression Of Brca2 In Epithelial Ovamentioning

confidence: 53%

“…Aberrant DNA methylation currently is recognized as a common molecular abnormality in cancer and it becomes potential molecular marker for diagnosis, prognosis and treatment (Laird, 2003). This finding has been reported and discussed in the previous studied for BRCA1 there were no correlation among BRCA1 methylation and BRCA1 expression with several clinocopathological factors such as; age, menarche, parity, menopauze status, BMI, CA125 level, clinical stage of disease, histopathological type, grade and residual tumor during surgery (Pradjatmo et al, 2014). Aberrant DNA methylation currently is recognized as a common molecular abnormality in cancer and it may be seen as potential molecular marker for diagnosis, prognosis and treatment (Laird, 2003).…”

Section: Brca2 Expression Induced Better Survivalmentioning

confidence: 85%

“…The protocols to study BRCA2 methylation status was following previously reported protocol for BRCA1 (Pradjatmo et al, 2014). The study design was a prospective cohort that was conducted at Sardjito Hospital, Yogyakarta, Indonesia.…”

Section: Clinical Samples Recruitmentmentioning

confidence: 99%

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Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers in Indonesia

Pradjatmo

2016

Asian Pacific Journal of Cancer Prevention

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Section: Brca2 Expression Induced Better Survivalsupporting

confidence: 66%

Section: Methylation Status and Expression Of Brca2 In Epithelial Ovamentioning

confidence: 53%

Section: Brca2 Expression Induced Better Survivalmentioning

confidence: 85%

Section: Clinical Samples Recruitmentmentioning

confidence: 99%

See 2 more Smart Citations

Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers in Indonesia

Pradjatmo

2016

Asian Pacific Journal of Cancer Prevention

Self Cite

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“…Besides germline and somatic mutations, epigenetic modifications like promoter hypermethylation of BRCA1 can also lead to downregulation of gene expression [3,4] and thus silencing of the BRCA1. Methylation of CpG islands in the BRCA1 promoter of primary high-grade ovarian carcinomas has been described ranging from 11-89% [1,[5][6][7][8]. The TCGA reported that epigenetic silencing of BRCA1 is mutually exclusive of BRCA1/2 mutations [1].…”

Section: Research Papermentioning

confidence: 99%

Loss of BRCA1 promotor hypermethylation in recurrent high grade ovarian cancer

Prieske

Joosse

Trillsch

et al. 2016

Geburtshilfe Frauenheilkd

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Background: Approximately 20-25% of ovarian cancers are attributable to germline or somatic BRCA1/2 mutations, resulting in defects in the homologous recombination pathway. Inactivation of these genes can also be mediated by epigenetic changes, e.g., hypermethylation of CpG islands in the promoter regions. In such homologous recombination deficient tumors, platinum based chemotherapy is in general effective, however, loss of hypermethylation might lead to refractory disease. The aim of this study was to evaluate the stability of BRCA1 promoter hypermethylation in recurrent disease after platinum based chemotherapy.Methods: Tumor tissue from 76 patients with primary and 48 patients with platinum-sensitive recurrent high-grade ovarian cancer was collected. In a subgroup of 12 patients, 'paired' tumor tissue from primary and recurrent surgery was available. BRCA1 promoter methylation status was assessed using methylation specific polymerase chain reaction and was verified by Sanger Sequencing.Results: 73.7% (56/76) of primary and 20.8% (10/48) of recurrent tumors displayed BRCA1 promoter hypermethylation. BRCA1 promoter methylation status was not associated with progression-free-or overall survival. In the paired subgroup 83.3% (10/12) of the primary vs. 16.7% (2/12) of the recurrent tumors showed hypermethylation. In eight patients loss of BRCA1 hypermethylation was observed, whereas two patients had stable methylation status.Conclusions: Loss of BRCA1 promoter methylation may be a mechanism to restore BRCA1 function in recurrent disease. However, currently the clinical significance is still unclear and should be evaluated in prospective clinical trials.

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BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer

et al. 2021

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Methylation of the BRCA1 promoter is an epigenetic gene expression regulator and is frequently observed in ovarian cancer; however, conversion of methylation status is thought to drive disease recurrence. Therefore, longitudinal monitoring of methylation status by liquid biopsy in cell-free DNA may be a predictive marker. In total, 135 plasma samples were collected from 69 ovarian cancer patients before and during systemic treatment. Our liquid biopsy assay could detect down to a single molecule of methylated DNA in a high background of normal DNA (0.03%) with perfect specificity in control samples. We found that 60% of the cancer patients exhibited BRCA1 promoter hypermethylation at one point, although 24% lost hypermethylation during treatment. Multivariate survival analyses indicate that relapses are independent events and that hypermethylation and methylation conversion are independently correlated to longer relapse-free survival. We present a highly sensitive and specific methylation-specific quantitative PCR-based liquid biopsy assay. BRCA1 promoter hypermethylation is frequently found in ovarian cancer and is often reversed upon recurrence, indicating the selection of therapy-resistant clones and unfavorable clinical outcome.

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Methylation Status and Immunohistochemistry of BRCA1 in Epithelial Ovarian Cancer

Cited by 13 publications

References 32 publications

Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers in Indonesia

Methylation Status and Expression of BRCA2 in Epithelial Ovarian Cancers in Indonesia

Loss of BRCA1 promotor hypermethylation in recurrent high grade ovarian cancer

BRCA1 promoter hypermethylation on circulating tumor DNA correlates with improved survival of patients with ovarian cancer

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