NDLI: Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast

Content Provider	Springer Nature Link
Author	Dallol, Ashraf Buhmeida, Abdelbaset Merdad, Adnan Al Maghrabi, Jaudah Gari, Mamdooh A. Abu Elmagd, Muhammad M. Elaimi, Aisha Assidi, Mourad Chaudhary, Adeel G. Abuzenadah, Adel M. Nedjadi, Taoufik Ermiah, Eramah Alkhayyat, Shadi S. Al Qahtani, Mohammed H.
Copyright Year	2015
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.
Starting Page	9677
Ending Page	9683
Page Count	7
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	36
Issue Number	12
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2015-07-08
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Breast cancer Methylation KLOTHO FGFR4 FGF19 Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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