Specific 50'CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patients.
Even after tremendous molecular studies, early detection,more accurate and sensitive diagnosis, and prognosis of breast cancer appear to be a riddle so far. To stab the enigma, this study is designed to envisage DNA methylation signatures as cancer-specific and stage-specific biomarkers in Indian patients. Rigorous review of scattered scientific reports on aberrant DNA methylation helped us to select and analyze a potential tumor suppressor gene pair (FHIT and p16 genes) in breast cancer patients. Methylation signatures from 232 primary sporadic breast cancer patients were pinpointed by methylation-specific PCR (MSP). To increase the sensitivity, we combined both MSP and expression studies (RT-PCR and Northern blotting) in a reproducible manner. Statistical analysis illustrated that hypermethylation of FHIT gene ( p < 0.0001) and p16 gene ( p=0.04) may be used as a potential diagnostic marker to diagnose the early and locally advanced stages of breast cancer. Additionally, the study authenticates the dependency of methylation and expressional loss of p16 gene on FHIT gene silencing. This observation not only describes the severity of disease when both genes are silenced but also drives to speculate the molecular cross talk between two genes or genetic pathways dictated by them separately.
Naqvi
Raza Ali
RA
Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Hussain
Arif
A
Raish
Mohmammad
M
Noor
Afshan
A
Shahid
Mohammad
M
Sarin
Ritu
R
Kukreti
Himani
H
Khan
Nida Jameel
NJ
Ahmad
Shandar
S
Deo
Suryanarayan V S
SV
Husain
Syed Akhtar
SA
Pasha
Syed Tazeen
ST
Basir
Seemi Farhat
SF
Shukla
Nootan Kumar
NK
D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000175:diagnosis*; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D019942:Genes, p16; D006801:Humans; D007194:India; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase