Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients.
Epigenetic mechanisms such as DNA methylation play important role in cancer. Epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prediction of disease prognosis. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for biomarker analyses. The aim of this study is to determine the correlation between methylation status of multiple cancer genes, p16(INK4A), p14(ARF), Cyclin D2 and Slit2 in invasive ductal carcinoma of the breast and paired serum DNA and clinicopathological parameters. Of the 36 breast cancer patients investigated, 31 (86%) tumors and 30 (83%) paired sera showed methylation of at least one of these 4 genes. Methylation frequencies varied from 27% for CyclinD2, 44% for p16(INK4A), 47% for p14(ARF) to 58% for Slit2. There was concordance between DNA methylation in tumor and paired serum DNA of each gene. This study underscores the potential utility of DNA methylation based screening of serum as a surrogate marker for tumor DNA methylation status of these genes in breast cancer. Further, expression profile of p16(INK4A) could be linked to epigenetic events, thus suggesting this pathway as a potential target for therapeutic strategies based on reversal of epigenetic silencing.
Sharma
Gayatri
G
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Mirza
Sameer
S
Prasad
Chandra P
CP
Srivastava
Anurag
A
Gupta
Siddhartha Dutta
SD
Ralhan
Ranju
R
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology*; D044967:Serum / Q000737:chemistry; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism; D000098552:Slit Homolog 2 Protein
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D025803:Tumor Suppressor Protein p14ARF; D051357:Cyclin-Dependent Kinase 2; D000098552:Slit Homolog 2 Protein