Role of BRCA1, HSD17B1 and HSD17B2 methylation in breast cancer tissue.
The pattern of altered gene expression due to epigenetic change is of major importance in malignancies. Aberrant DNA methylation is one of the many potential causes for this and is considered to be an early event in the etiology of breast carcinogenesis. The present study assessed the methylation status of three genes relevant in breast cancer (BC): The breast cancer susceptibility gene 1 (BRCA1), 17 beta hydroxy steroid dehydrogenase type 1 (HSD17B1) and type 2 (HSD17B2). Restriction enzyme based Methylation specific PCR (REMS PCR) was carried out in 104 tumor samples from sporadic BC patients and 48 samples of adjacent normal breast tissue. The percentage of tumor samples showing BRCA1, HSD17B1 and HSD17B2 methylation was 20.4%, 83.3% and 31.3%, respectively. Methylation was higher in tumors when compared to adjacent normal breast tissue samples. This suggests that methylation of these three genes plays an important role in BC etiology. Methylation is responsible for gene silencing and since BRCA1 and HSD17B2 were not found to be methylated in the same tissue samples, this suggests that the etiology of > 50% of the tumors could be accounted for by the independent epigenetic silencing of these two genes. BRCA1 and HSD17B2 genes may increase the risk of developing BC via enhanced estradiol activity. It is for the first time that the role of HSD17B gene methylation in BC pathophysiology is being proposed.
Bhavani
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V
Department of Genetics, Vasavi Hospital and Research Centre, Khairtabad, Hyderabad, India.
Srinivasulu
M
M
Ahuja
Y R
YR
Hasan
Q
Q
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004960:Estradiol Dehydrogenases / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D008875:Middle Aged
D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human