Specific 5′CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patients

Raza A Naqvi, Arif Hussain, Mohmammad Raish, Afshan Noor, Mohammad Shahid, Ritu Sarin, Himani Kukreti, Nida Jameel Khan, Shandar Ahmad, Suryanarayan V.S. Deo, Syed Akhtar Husain, Syed Tazeen Pasha, Seemi Farhat Basir, Nootan Kumar Shukla

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)517-525
Number of pages9
JournalDNA and Cell Biology
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2008

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