Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.27.1 (
RNase
)
16,360
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
HIC-1
(hypermethylated in cancer) is a candidate tumor suppressor gene which is located at 17p13.3, a region which frequently undergoes allelic loss in breast and other human cancers.
HIC-1
is proposed to be commonly inactivated in human cancers by hypermethylation of a normally unmethylated dense CpG island which encompasses the entire gene. To study whether
HIC-1
inactivation may be important to the development of breast cancer, we first measured methylation of the
HIC-1
gene in normal breast ductal tissues from microdissected frozen breast tissues and from epithelial cells purified from mammoplasty specimens. Surprisingly, in all normal breast ductal tissues we found approximately equal amounts of densely methylated
HIC-1
and completely unmethylated
HIC-1
. This is in contrast to most normal tissues, in which all copies of
HIC-1
are completely unmethylated. We then evaluated 39 primary breast cancer tissues and found virtually complete methylation of the
HIC-1
gene in 26 (67%) of the cases. We also found loss of heterozygosity at the telomeric portion of chromosomal arm 17p in 22 of the 26 cases with strongly methylated
HIC-1
, suggesting that loss of an unmethylated
HIC-1
allele may contribute to the inactivation of
HIC-1
in cells with a pre-existing methylated allele. Finally, by
RNase
protection analysis,
HIC-1
was found to be expressed in microdissected normal breast ductal tissues and unmethylated tumors but not in tumors with hypermethylation of the
HIC-1
gene. These results indicate that hypermethylation of
HIC-1
and associated loss of
HIC-1
expression is common in primary breast cancer. Furthermore, the
HIC-1
gene is densely methylated in approximately one-half of the alleles in normal breast epithelium, which may predispose this tissue to inactivation of this gene by loss of heterozygosity.
...
PMID:Methylation of the HIC-1 candidate tumor suppressor gene in human breast cancer. 957 97
