Promoter hypermethylation of TMS1, BRCA1, ERα and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients

Mirza, Sameer; Sharma, Gayatri; Prasad, Chandra Prakash; Parshad, Rajinder; Srivastava, Anurag; Gupta, Siddhartha Dutta; Ralhan, Ranju

doi:10.1016/j.lfs.2007.05.012

Cited by 101 publications

(83 citation statements)

References 40 publications

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“…Recently, several groups, using a panel of multiple genes which are well known to be tumorassociated, have demonstrated the prevalence of methylation positive genes in sera or plasma from breast cancer patients (20)(21)(22)(23)(24)(25)(26)(27). Nevertheless, current multiple gene panel assays still lack the necessary sensitivity for application in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Kim¹,

Lee

Oh³

et al. 2012

Oncol Rep

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Abstract. Aberrant DNA methylation occurs early and frequently in tumorigenesis. Identification of DNA methylation biomarkers is a field that provides potential for improving the clinical process of breast cancer diagnosis. We utilized a genome-wide technique, methylated DNA isolation assay (MeDIA), in combination with high-resolution CpG microarray analysis to identify hypermethylated genes in breast cancer. Among differentially methylated genes between tumor and adjacent normal tissues, 3 candidate genes (LHX2, WT1 and OTP) were finally selected through a step-wise filtering process and examined for methylation status in normal tissues, primary tumor, and paired adjacent normal-appearing tissues from 39 breast cancer patients. Based on the calculated cut-off values, all genes showed significantly higher frequencies of aberrant hypermethylation in primary tumors (43.6% for LHX2, 89.7% for WT1 and 100% for OTP, P<0.05) while frequencies were intermediate in paired adjacent normal tissues and absent in normal tissues. On further analysis, the methylation level in primary tumors was not significantly correlated with clinicopathological features. Interestingly, DNA methylation of a novel gene OTP was detected in adjacent normal tissues even 6 cm away from primary tumors, suggesting that OTP methylation may qualify as a biomarker for the early detection of breast cancer. In conclusion, we successfully identified a novel gene OTP frequently methylated in breast cancer by genomewide screening. Our results suggest that the OTP gene may play a crucial role in breast carcinogenesis, although further clinical validation will be needed to evaluate the potential application of OTP in the early detection of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Kim¹,

Lee

Oh³

et al. 2012

Oncol Rep

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show abstract

“…In addition to these highly characterized mutations, epigenetic alterations resulting in aberrant gene expression are key contributor to breast tumorigenesis (Campan et al, 2006;Giacinti et al, 2006;Mirza et al, 2007;Sharma et al, 2005;Sui et al, 2007;VincentSalomon et al, 2007;Visvanathan et al, 2006;Zhou et al, 2006. Decreased methylation of repetitive sequences in the satellite DNA of the pericentric region of chromosomes is associated with increased chromosomal rearrangements, mitotic recombination, and aneuploidy (Eden et al, 2003,Karpf andMatsui, 2005).…”

Section: Dna Methylation and Breast Cancermentioning

confidence: 99%

“…Furthermore, BRCA1 is a tumor suppressor gene for both breast and ovarian cancer (Campan et al, 2006). It encodes a multifunctional protein with roles in DNA repair, cell cycle check point control, protein ubiquitization, and chromatin remodeling (Mirza et al, 2007). In vitro experiments showed that decreased BRCA1 expression in cells led to increased levels of tumor growth, while increased expression of BRCA1 led to growth arrest and apoptosis.…”

Section: Breast Cancer Epigenetic Markersmentioning

confidence: 99%

“…Recent studies indicate that BRCA1 methylation is an important marker for prognosis. The magnitude of the decrease of functional BRCA1 protein correlates with disease prognosis (Mirza et al, 2007;Vincent-Salomon et al, 2007). Tumors with BRCA1 mutations are usually more likely to be higher-grade, poorly differentiated, highly proliferative, estrogen receptor (ER) negative, and progesterone receptor (PR) negative, and harbor p53 mutations.…”

Section: Breast Cancer Epigenetic Markersmentioning

confidence: 99%

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Epigenetics and Breast Cancer

Alokail¹

2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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“…Furthermore, aberrant promoter methylation of cancerrelated genes, such as ER-α in sporadic breast tumors and their nonrandom distributions has also been investigated (Parrella et al, 2004). The different frequencies of ER-α gene silencing via promoter hypermethylation have been reported in Chinese (Zhao et al, 2008), Turkish (Buyru et al, 2009), North American and Korean (Lee et al, 2008), American (Wei et al, 2008), and Indian (Mirza et al, 2007) women with breast cancer, thus revealing the diverse impact on the prognosis of cancer. As far as the methylation status of ER-α has not been mapped in triple negative tumors and its impact has not been compared with non-triple negative tumors, current study was sought to evaluate the hypermethylation pattern of CpGs across the ER gene CpG island in Iranian females with triple negative and non-triple negative breast tumors and impact of methylation profile in the clinicopathological features.…”

Section: Introductionmentioning

confidence: 99%

CpG Island Methylation Profile of Estrogen Receptor Alpha in Iranian Females with Triple Negative or Non-triple Negative Breast Cancer: New Marker of Poor Prognosis

Ramezani

Salami²,

Omrani³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of estrogen receptor (ER) gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-2 + overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-2 + tumors and in postmenopausal patients with ER¯, PgR¯, or ER¯/PgR¯ tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre-and postmenopausal patients. Findings revealed that aberrant hypermethylation of the ER-alpha gene frequently occurs in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.

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Promoter hypermethylation of TMS1, BRCA1, ERα and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients

Cited by 101 publications

References 40 publications

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Genome-wide identification of OTP gene as a novel methylation marker of breast cancer

Epigenetics and Breast Cancer

CpG Island Methylation Profile of Estrogen Receptor Alpha in Iranian Females with Triple Negative or Non-triple Negative Breast Cancer: New Marker of Poor Prognosis

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