PMID- 9187126
OWN - NLM
STAT- MEDLINE
DCOM- 19970710
LR  - 20220317
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 57
IP  - 11
DP  - 1997 Jun 1
TI  - Extensive DNA methylation spanning the Rb promoter in retinoblastoma tumors.
PG  - 2229-37
AB  - The retinoblastoma gene (Rb) is one of the best characterized tumor suppressor 
      genes, and its inactivation is associated with a number of cancers. Previous 
      studies have shown, by restriction enzyme analysis, that the promoter region of 
      the Rb gene is methylated in a significant proportion of primary retinoblastoma 
      tumors. We now report the first detailed methylation sequence analysis of the CpG 
      island spanning the retinoblastoma promoter from hypermethylated retinoblastoma 
      tumors. Our results show methylation is not confined to a specific CpG site, as 
      detected by restriction enzyme studies, but extends to essentially all 27 CpG 
      dinucleotides spanning the retinoblastoma CpG island, including the core 
      promoter. The methylation pattern from each tumor DNA sample is different, 
      ranging from densely to sparsely methylated profiles. Single CpG sites, in 
      particular the E2F transcription factor binding site, as well as blocks of CpGs, 
      were undermethylated in some tumor samples. Possible interference of methylation 
      could be due to the binding of sequence-specific protein factors at these sites 
      in the tumor cells. This study highlights that the dynamics of DNA methylation in 
      cancer cells are clearly different from normal cells and gives an insight into 
      the mechanism of abnormal methylation of CpG islands in cancer cells.
FAU - Stirzaker, C
AU  - Stirzaker C
AD  - Kanematsu Laboratories, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
FAU - Millar, D S
AU  - Millar DS
FAU - Paul, C L
AU  - Paul CL
FAU - Warnecke, P M
AU  - Warnecke PM
FAU - Harrison, J
AU  - Harrison J
FAU - Vincent, P C
AU  - Vincent PC
FAU - Frommer, M
AU  - Frommer M
FAU - Clark, S J
AU  - Clark SJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Base Sequence
MH  - Blotting, Southern
MH  - *Carrier Proteins
MH  - *Cell Cycle Proteins
MH  - Cloning, Molecular
MH  - CpG Islands
MH  - *DNA Methylation
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - Eye Neoplasms/*genetics
MH  - Female
MH  - *Genes, Retinoblastoma
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - *Promoter Regions, Genetic
MH  - Retinoblastoma/*genetics
MH  - Retinoblastoma-Binding Protein 1
MH  - Sequence Analysis, DNA
MH  - Transcription Factor DP1
MH  - Transcription Factors/genetics
EDAT- 1997/06/01 00:00
MHDA- 1997/06/01 00:01
CRDT- 1997/06/01 00:00
PHST- 1997/06/01 00:00 [pubmed]
PHST- 1997/06/01 00:01 [medline]
PHST- 1997/06/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1997 Jun 1;57(11):2229-37.