title: Promoter Hypermethylation in Tumor Suppressing Genes p16 and FHIT and Their Relationship with Estrogen Receptor and Progesterone Receptor Status in Breast Cancer Patients from Northern India.
abstract: BACKGROUND
  Aberrant DNA methylation has been recognized in human breast carcinogenesis as a common molecular alteration associated with the loss of expression of a number of key regulatory genes. The present study was undertaken to determine whether methylation and expression of p16 and FHIT genes would correlate with the estrogen receptor (ER) and progesterone receptor (PR) status.
  
  
  METHODS
  Methylation-specific polymerase chain reaction, messenger RNA (mRNA) expression analysis, immunohistochemistry, and Western blot analysis were performed to study the methylation of p16 and FHIT genes in 351 pairs of malignant/normal breast tissues. We examined the expression of ER and PR in those specimens by immunohistochemistry. Mutations of p16 and FHIT genes in tumors were detected by direct sequencing.
  
  
  RESULTS
  The frequency of hypermethylation was 31.9% and 36.8% in p16 and FHIT genes, respectively, and showed significant harmony in concordant hypermethylation (P < .0001). In postmenopausal patients, methylation frequency in both genes is significantly higher in poorly and moderately differentiated tumors. Loss of protein expression of p16 and FHIT in 77 and 74 tumors, respectively, is associated with their methylation status in premenopausal women.
  
  
  CONCLUSIONS
  We did not find any significant differences in tumor-related gene methylation patterns relevant to both ER and PR status of breast tumors.
authors: Human Genetics Lab, Jamia Millia Islamia, New Delhi-110025, India.
authors: Mohammad
authors: M
authors: Raish
authors: Varinderpal S
authors: VS
authors: Dhillon
authors: Arif
authors: A
authors: Ahmad
authors: Mushtaq Ahmad
authors: MA
authors: Ansari
authors: Shahid
authors: S
authors: Mudassar
authors: Mohammad
authors: M
authors: Shahid
authors: Vineeta
authors: V
authors: Batra
authors: Pawan
authors: P
authors: Gupta
authors: Bhudev Chandra
authors: BC
authors: Das
authors: Nk
authors: N
authors: Shukla
authors: Syed Akhtar
authors: SA
authors: Husain