| Title |
Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast
|
|---|---|
| Published in |
Tumor Biology, July 2015
|
| DOI | 10.1007/s13277-015-3733-3 |
| Pubmed ID | |
| Authors |
Ashraf Dallol, Abdelbaset Buhmeida, Adnan Merdad, Jaudah Al-Maghrabi, Mamdooh A. Gari, Muhammad M. Abu-Elmagd, Aisha Elaimi, Mourad Assidi, Adeel G. Chaudhary, Adel M. Abuzenadah, Taoufik Nedjadi, Eramah Ermiah, Shadi S. Alkhayyat, Mohammed H. Al-Qahtani |
| 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. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 18% |
| Professor > Associate Professor | 4 | 12% |
| Student > Postgraduate | 3 | 9% |
| Researcher | 2 | 6% |
| Student > Master | 2 | 6% |
| Other | 6 | 18% |
| Unknown | 11 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 8 | 24% |
| Biochemistry, Genetics and Molecular Biology | 7 | 21% |
| Agricultural and Biological Sciences | 3 | 9% |
| Nursing and Health Professions | 2 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 11 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 July 2015.
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#20,282,766
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#1,834
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#218,971
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Outputs of similar age from Tumor Biology
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