title: Specific 50'CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patients.
abstract: 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.
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
authors.forename: Raza Ali
authors.initials: RA
authors.lastname: Naqvi
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
authors.forename: Mohmammad
authors.initials: M
authors.lastname: Raish
authors.forename: Afshan
authors.initials: A
authors.lastname: Noor
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahid
authors.forename: Ritu
authors.initials: R
authors.lastname: Sarin
authors.forename: Himani
authors.initials: H
authors.lastname: Kukreti
authors.forename: Nida Jameel
authors.initials: NJ
authors.lastname: Khan
authors.forename: Shandar
authors.initials: S
authors.lastname: Ahmad
authors.forename: Suryanarayan V S
authors.initials: SV
authors.lastname: Deo
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
authors.forename: Syed Tazeen
authors.initials: ST
authors.lastname: Pasha
authors.forename: Seemi Farhat
authors.initials: SF
authors.lastname: Basir
authors.forename: Nootan Kumar
authors.initials: NK
authors.lastname: Shukla
mesh_terms: 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
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase