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.
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.
Raish
Mohammad
M
Human Genetics Lab, Jamia Millia Islamia, New Delhi-110025, India.
Dhillon
Varinderpal S
VS
Ahmad
Arif
A
Ansari
Mushtaq Ahmad
MA
Mudassar
Shahid
S
Shahid
Mohammad
M
Batra
Vineeta
V
Gupta
Pawan
P
Das
Bhudev Chandra
BC
Shukla
Nk
N
Husain
Syed Akhtar
SA