title: A study on promoter methylation of PTEN in sporadic breast cancer patients from North India.
abstract: BACKGROUND
  Epigenetic silencing of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) through DNA methylation has been implicated in the pathogenesis of breast cancer. Present study investigates the contribution of PTEN promoter methylation and its associated protein expression in sporadic breast cancer patients from North India.
  
  
  METHODS
  A total of 360 paired breast carcinoma and adjacent normal tissue samples from 180 sporadic breast cancer patients were included in the present study and examined for PTEN promoter methylation status by methylation-specific polymerase chain reaction. Immunohistochemistry method was used for determining PTEN protein expression. Molecular findings were statistically correlated with various clinicopathological parameters to identify associations of clinical relevance.
  
  
  RESULTS
  Presence of PTEN promoter methylation (39.44 %) significantly correlated with its expression downregulation (45.56 %) in breast tumors (P = 0.0001). Furthermore, their interaction with various clinical parameters was evidenced in stratified analysis. Correlation of PTEN promoter methylation with histologically more malignant grade and PTEN expression loss with triple negative tumor status remained significant even after Bonferroni correction (P < 0.003).
  
  
  CONCLUSIONS
  Results implicate promoter methylation to be a mechanism partially responsible for PTEN silencing in sporadic breast cancer for North Indian women. Besides, methylation and expression loss of PTEN exhibited promising potential as candidate biomarkers of risk assessment in subcategorized breast tumors with critical pathologic parameters.
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Sarah
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Naseem
authors.initials: N
authors.lastname: Akhter
authors.affiliation: Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: S V S
authors.initials: SV
authors.lastname: Deo
authors.affiliation: Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, 110029, India.
authors.forename: N K
authors.initials: NK
authors.lastname: Shukla
authors.affiliation: Department of Biosciences, Jamia Millia Islamia, New Delhi, 110025, India. akhtarhusain2000@yahoo.com.
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007194:India; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Breast cancer; PTEN; Promoter methylation; Protein expression