Aberrant methylation of RASSF1A is associated with poor survival in Tunisian breast cancer patients

Karray-Chouayekh, Sondes; Trifa, Fatma; Khabir, Abdelmajid; Boujelbane, Nouredine; Sellami‐Boudawara, Tahya; Daoud, J.; Frikha, M.; Jlidi, R.; Gargouri, Ali; Mokdad-Gargouri, Raja

doi:10.1007/s00432-009-0649-6

Cited by 36 publications

(43 citation statements)

References 34 publications

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“…As far as the two major histological subtypes are concerned, a similar frequency of methylation was detected as previously reported (6,29,34). Interestingly, a statistically-significant relationship between RASSF1A promoter methylation and advanced T-category was found in accordance to Karray-Chouayekh et al (35) suggesting its involvement as a late event in breast tumourigenesis. On the other hand, Kioulafa et al (33) reported a correlation of RASSF1A promoter methylation with early tumour stages.…”

Section: Discussionsupporting

confidence: 86%

Association of aberrant DNA methylation with clinicopathological features in breast cancer

Tserga

Michalopoulos²,

Levidou³

et al. 2011

Oncol Rep

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Abstract. Aberrant DNA methylation is responsible for the epigenetic silencing of genes associated with tumourigenesis and progression of cancer. In this study, we assessed the methylation status of eight genes in 49 snap-frozen primary breast tumours. Epigenetic alterations of 8 genes were analysed with methylation-specific polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or methylationsensitive high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1 and PTEN). MS-HRM performance was validated by bisulfite pyrosequencing regarding the methylation levels of MGMT. Promoter methylation was observed in APC 54.34%, 40.4% DCR1, 37.5% DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0% DCR2 promoters, respectively. Interestingly, 37 out of 49 cases (75.5%) displayed aberrant promoter methylation in at least one gene. An association of MGMT promoter methylation with age and tumour grade was recorded. Moreover, a correlation with advanced T-category was elicited for GSTP1, RASSF1 and DAPK1 promoter methylation. Finally, concurrent methylation of several genes showed a marginal statistical relationship with N-category. We conclude that APC, DCR1, DAPK1 and RASSF1A promoter methylation represents a common event in breast cancer tumourigenesis. Our results suggest that GSTP1, RASSF1, DAPK1 and MGMT may be implicated in the acquisition of a more aggressive phenotype in breast cancer.

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Section: Discussionsupporting

confidence: 86%

Association of aberrant DNA methylation with clinicopathological features in breast cancer

Tserga

Michalopoulos²,

Levidou³

et al. 2011

Oncol Rep

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“…Further, a meta-analysis by Fang et al [34] reported that the methylation rate of RARβ2 is significantly increased among breast cancer patients compared to cancer-free controls. In a report from Russia, methylated RARβ2 was found to be 3 times more frequent in breast cancer patients than in fibroadenoma patients [35]. In contrast, a lack of association between the methylation status of RARβ2 and breast cancer risk has been reported in Russian [21], American [35], Turkish [36], and Senegalese [37] populations.…”

Section: Discussionmentioning

confidence: 98%

“…In a report from Russia, methylated RARβ2 was found to be 3 times more frequent in breast cancer patients than in fibroadenoma patients [35]. In contrast, a lack of association between the methylation status of RARβ2 and breast cancer risk has been reported in Russian [21], American [35], Turkish [36], and Senegalese [37] populations. Also, some studies found a lack of concordance between RARβ2 methylation in tumor tissue and paired WBC, suggesting that there might not be a direct link between WBC gene methylation and development of breast cancer (table 3).…”

Section: Discussionmentioning

confidence: 98%

Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Yari¹,

Rahimi

2019

Breast Care

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Background: We aimed to determine the promoter methylation status of the retinoic acid receptor-beta 2 (RARβ2) gene among breast cancer patients and to review relevant studies in this field in various populations. Methods: We analyzed 400 samples which comprised blood specimens from 102 breast cancer patients, 102 first-degree female relatives of patients, 100 cancer-free females, 48 breast cancer tissues, and 48 adjacent normal breast tissues from the same patients. The RARβ2 methylation status was determined using methylation-specific polymerase chain reaction (MSP) and DNA sequencing methods. Results: The presence of combined partially methylated (MU) and fully methylated (MM) forms of the RARβ2 gene (MU+MM) in the blood of patients was associated with susceptibility to breast cancer (odds ratio = 4.7, p = 0.05). A significantly higher frequency of the MM genotype was observed in cancer tissue (10.4%) compared to matched adjacent normal breast tissue (0%) (p = 0.02). Conclusion: We found a higher frequency of RARβ2 gene methylation in the blood and cancer tissues of patients compared to the blood of controls and adjacent normal breast tissues. The survey of studies on various populations demonstrated a higher RARβ2 methylation frequency in breast cancer patients compared to normal individuals, and many reports suggest a significant association between hypermethylation of the gene and susceptibility to breast cancer.

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“…Of these genes Cyclin D2 exhibited a stark contrast in frequency between AAs (64%) and Caucasians (19%). While some of these genes may not be linked to prognosis, hypermethylation of Cyclin D2 and RASSF1A are both associated with higher relapse rates and poor overall survival (91)(92)(93).…”

Section: Insights From Other Cancersmentioning

confidence: 99%

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

Lerner¹,

Winn²,

Hulbert³

2018

J. Thorac. Dis.

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Lung cancer is the most prominent cause of cancer-related mortality. Significant disparities in incidence and outcome characterize the disease's manifestations among ethnically and racially diverse populations. Complete surgical resection is the most effective curative treatment. However, success relies on early tumor detection. The National Lung Cancer Screening trial showed that lung cancer related mortality can be reduced by the use of low-dose CT (LDCT) screening. However, this test is plagued by a high false positive rate of 97% and the device itself is limited to designated cancer centers due to its expense and size. This restriction makes it difficult for underserved groups to access LDCT screening, the current standard of care. Highly sensitive and specific epigenetic DNA methylation-based biomarkers have the potential to work independently or in conjunction with LDCT screening to identify early-stage tumors. These tests could reduce unnecessary invasive confirmatory diagnostic tests and their associated morbidity and mortality.These tests also have the opportunity to bring lung cancer screening to the community thereby reducing unequal accessibility. However, epigenetic alterations are closely linked to the interplay between hereditary and environmental factors such as diet, lifestyle, ethnic ancestry, toxin exposure, residential segregation, and disparate community support structures. Despite this, the overwhelming number of early detection DNA methylation biomarker studies to date have either failed to control for ethnicity or have employed heavily Caucasian-biased patient cohorts. This review seeks to summarize the literature related to the early detection of lung cancer through molecular biomarkers among different ethnicities. Ethnical specific epigenetic biomarkers have the potential to be the first step towards an accessible, available personalized medicine approach to cancer through liquid biopsy.

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Aberrant methylation of RASSF1A is associated with poor survival in Tunisian breast cancer patients

Abstract: Our preliminary findings suggested that aberrant methylation of RASSF1A and RARbeta2 occurs frequently in Tunisian breast cancer patients compared with others. Furthermore, RASSF1A hypermethylation could be used as a potential marker of poor prognosis.

Cited by 36 publications

References 34 publications

Association of aberrant DNA methylation with clinicopathological features in breast cancer

Association of aberrant DNA methylation with clinicopathological features in breast cancer

Promoter Methylation Status of the Retinoic Acid Receptor-Beta 2 Gene in Breast Cancer Patients: A Case Control Study and Systematic Review

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

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