PMID- 10369881
OWN - NLM
STAT- MEDLINE
DCOM- 19990816
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 7
DP  - 1999 Jul
TI  - Multipoint analysis of human chromosome 11p15/mouse distal chromosome 7:
      inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19
      silencing in Wilms' tumorigenesis and methylation hyper-dependence of H19
      imprinting.
PG  - 1337-52
AB  - WT2 is defined by maternal-specific loss of heterozygosity (LOH) on chromosome
      11p15.5 in Wilms' tumors (WTs). The imprinted H19 gene, in this region, is
      silenced and hypermethylated in most WTs, and this is linked to pathological
      biallelic expression of IGF2. However, H19 and IGF2 lie within a larger imprinted
      domain, and the gene specificity of H19 epimutation has been a persistent
      question. To address this, we assessed LOH, gene expression and DNA methylation
      at multiple sites in and around the imprinted domain. LOH mapping showed that the
      entire domain, including IGF2/H19, is within the minimal WT2 region. Genes within
      the domain, including IPL/TSSC3/BWR1C, IMPT1/ORCTL2/BWR1A/TSSC5, KvLQT1/KCNA9 and
      TAPA1/CD81, as well as the zinc finger gene ZNF195/ZNFP104 near the centromeric
      border, were expressed persistently in many WTs. DNA hypermethylation was not
      detected with 5" upstream probes for IPL, IMPT1, KvLQT1 and ZNF195 in WTs or
      WT-associated kidneys. Fully developed WTs showed variable hypomethylation at an 
      imprinted CpG island in a KvLQT1 intron, but this was only complete in the cases 
      with LOH and was not observed in pre-neoplastic WT-associated kidneys with H19
      epimutation. Analysis of the corresponding region of mouse chromosome 7 using
      methyltransferase-hypomorphic mice showed that the H19 imprint was fully erased, 
      but that the allelic bias at Ipl, Impt1, p57 Kip2 and, to a lesser extent,
      Kvlqt1, persisted. Pre-existing massive allelic asymmetry for DNA methylation and
      hyper-dependence of transcription on methylation status may underlie the
      mechanism of gene-specific silencing of H19 in Wilms' tumorigenesis.
FAU - Dao, D
AU  - Dao D
AD  - Department of Pathology and Institute for Cancer Genetics, Columbia Univesity
      College of Physicians and Surgeons, New York, NY 10032, USA.
FAU - Walsh, C P
AU  - Walsh CP
FAU - Yuan, L
AU  - Yuan L
FAU - Gorelov, D
AU  - Gorelov D
FAU - Feng, L
AU  - Feng L
FAU - Hensle, T
AU  - Hensle T
FAU - Nisen, P
AU  - Nisen P
FAU - Yamashiro, D J
AU  - Yamashiro DJ
FAU - Bestor, T H
AU  - Bestor TH
FAU - Tycko, B
AU  - Tycko B
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (H19 long non-coding RNA)
RN  - 0 (Muscle Proteins)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (RNA, Neoplasm)
RN  - 0 (RNA, Untranslated)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
SB  - IM
MH  - Animals
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 11
MH  - DNA Methylation
MH  - *Genes, Wilms Tumor
MH  - *Genomic Imprinting
MH  - Humans
MH  - Insulin-Like Growth Factor II/genetics
MH  - Kidney/physiopathology
MH  - Loss of Heterozygosity
MH  - Mice
MH  - Muscle Proteins/biosynthesis/*genetics
MH  - RNA, Long Noncoding
MH  - RNA, Neoplasm/biosynthesis
MH  - *RNA, Untranslated
MH  - Wilms Tumor/etiology/*genetics
EDAT- 1999/06/17 00:00
MHDA- 1999/06/17 00:01
CRDT- 1999/06/17 00:00
PHST- 1999/06/17 00:00 [pubmed]
PHST- 1999/06/17 00:01 [medline]
PHST- 1999/06/17 00:00 [entrez]
AID - ddc147 [pii]
AID - 10.1093/hmg/8.7.1337 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Jul;8(7):1337-52. doi: 10.1093/hmg/8.7.1337.