EPIGENETIC LESIONS AT THE H19 LOCUS IN WILMS-TUMOR PATIENTS

被引：318
作者：
MOULTON, T
CRENSHAW, T
HAO, Y
MOOSIKASUWAN, J
LIN, N
DEMBITZER, F
HENSLE, T
WEISS, L
MCMORROW, L
LOEW, T
KRAUS, W
GERALD, W
TYCKO, B
机构：
[1] COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,DIV ONCOL,NEW YORK,NY 10032
[2] COLUMBIA UNIV,COLL PHYS & SURG,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,NEW YORK,NY 10032
[3] COLUMBIA UNIV,COLL PHYS & SURG,DEPT PATHOL,DIV NEUROPATHOL,NEW YORK,NY 10032
[4] COLUMBIA UNIV,COLL PHYS & SURG,DEPT SURG,DIV PEDIAT SURG,NEW YORK,NY 10032
[5] CITY HOPE NATL MED CTR,DEPT PATHOL,DUARTE,CA 91010
[6] UNIV MED & DENT NEW JERSEY,COOPER HOSP,MED CTR,DEPT PEDIAT,DIV HEMATOL ONCOL,CAMDEN,NJ 08103
[7] SO ILLINOIS UNIV,SCH MED,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL,SPRINGFIELD,IL 62702
[8] SCOTTISH RITE CHILDRENS HOSP,DEPT PEDIAT,DIV GENET,ATLANTA,GA 30342
[9] MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021
来源：
NATURE GENETICS | 1994年 / 7卷 / 03期
关键词：
D O I：
10.1038/ng0794-440
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.
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页码：440 / 447
页数：8
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