Clinical significance of promoter hypermethylation of RASSF1A, RARbeta2, BRCA1 and HOXA5 in breast cancers of Indian patients.
Promoter hypermethylation of genes is implicated in the pathogenesis of many cancers, including breast cancer. Herein, we analyzed the promoter methylation status of a panel of critical growth regulatory genes, RASSF1A, RARbeta2, BRCA1 and HOXA5, in 54 breast cancers and 5 distant normal breast tissues of Indian patients. The methylation data were correlated with clinicopathological characteristics and hormone receptor status to determine the impact of methylation in breast carcinogenesis. Promoter hypermethylation of RASSF1A was observed in 39/54 (72%), HOXA5 in 36/54 (67%), BRCA1 in 15/54 (28%) and RARbeta2 in 8/54 (15%) breast cancers. Our most significant findings were the association of RASSF1A methylation with nodal metastasis (p=0.05); and RARbeta2 methylation with age (all tumors in patients in the older age group were methylated, p=0.04). Further, the interactions between DNA methylation and hormone receptor biology in breast cancer cells are beginning to be clearly understood. In this context the association of HOXA5 methylation with loss of ERalpha (p=0.009) is noteworthy.
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Sarangadhara Appala Raju
SA
Bagadi
Chandra Prakash
CP
Prasad
Jatinder
J
Kaur
Anurag
A
Srivastava
Rajinder
R
Prashad
Siddartha Datta
SD
Gupta
Ranju
R
Ralhan
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D052138:Genes, Neoplasm; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D019313:BRCA1 Protein; C489213:HOXA5 protein, human; D018398:Homeodomain Proteins; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta