Document Details

Document Type : Article In Journal 
Document Title :
Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast
Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast
 
Document Language : English 
Abstract : Invasive ductal carcinoma of the breast is the most common cancer affecting women worldwide. The marked heterogeneity of breast cancer is matched only with the heterogeneity in its associated or causative factors. Breast cancer in Saudi Arabia is apparently an early onset with many of the affected females diagnosed before they reach the age of 50 years. One possible rationale underlying this observation is that consanguinity, which is widely spread in the Saudi community, is causing the accumulation of yet undetermined cancer susceptibility mutations. Another factor could be the accumulation of epigenetic aberrations caused by the shift toward a Western-like lifestyle in the past two decades. In order to shed some light into the molecular mechanisms underlying breast cancer in the Saudi community, we identified KLOTHO (KL) as a tumor-specific methylated gene using genome-wide methylation analysis of primary breast tumors utilizing the MBD-seq approach. KL methylation was frequent as it was detected in 55.3 % of breast cancer cases from Saudi Arabia (n = 179) using MethyLight assay. Furthermore, KL is downregulated in breast tumors with its expression induced following treatment with 5-azacytidine. The involvement of KL in breast cancer led us to investigate its relationship in the context of breast cancer, with one of the protagonists of its function, fibroblast growth factor receptor 4 (FGFR4). Overexpression of FGFR4 in breast cancer is frequent in our cohort and this overexpression is associated with poor overall survival. Interestingly, FGFR4 expression is higher in the absence of KL methylation and lower when KL is methylated and presumably silenced, which is suggestive of an intricate relationship between the two factors. In conclusion, our findings further implicate "metabolic" genes or pathways in breast cancer that are disrupted by epigenetic mechanisms and could provide new avenues for understanding this disease in a new context. 
ISSN : 1423-0380 
Journal Name : Tumour Biol 
Volume : 36 
Issue Number : 12 
Publishing Year : 1436 AH
2015 AD 
Article Type : Article 
Added Date : Tuesday, April 19, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Ashraf DallolDallol, Ashraf Investigator adallol@kau.edu.sa
Abdelbaset BuhmeidaBuhmeida, Abdelbaset Researcher  
Adnan MerdadMerdad, Adnan Researcher  
Jaudah Al-MaghrabiAl-Maghrabi, Jaudah Researcher  
Mamdooh A. GariGari, Mamdooh A.Researcher  
Muhammad M. Abu-ElmagdAbu-Elmagd, Muhammad M.Researcher  
Aisha ElaimiElaimi, Aisha Researcher  
Mourad AssidiAssidi, Mourad Researcher  
Adeel G. ChaudharyChaudhary, Adeel G.Researcher  
Adel M. AbuzenadahAbuzenadah, Adel M.Researcher  
Taoufik NedjadiNedjadi, Taoufik Researcher  
Eramah ErmiahErmiah, Eramah Researcher  
Shadi S. AlkhayyatAlkhayyat, Shadi S.Researcher  
Mohammed H. Al-QahtaniAl-Qahtani, Mohammed H.Researcher  

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