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| LOSS OF IMPRINTING OF IGF2 IS LINKED TO REDUCED EXPRESSION AND ABNORMAL METHYLATION OF H19 IN WILMS-TUMOR |
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| Author(s): STEENMAN MJC, RAINIER S, DOBRY CJ, GRUNDY P, HORON IL, FEINBERG AP |
| Source: NATURE GENETICS Volume: 7 Issue: 3 Pages: 433-439 Published: JUL 1994 |
| Times Cited: 321 References: 54 |
| Abstract: The insulin-like growth factor-II (IGF2) and H19 genes are imprinted in mouse and human, with expression of the paternal IGF2 and maternal H19 alleles. IGF2 undergoes loss of imprinting (LOI) in most Wilms' tumours (WT). We now show that: (i) LOI of IGF2 is associated with a 80-fold down regulation of H19 expression; (ii) these changes are associated with alterations in parental-origin-specific, tissue-independent sites of DNA methylation in the H19 promoter; and (iii) loss of heterozygosity is also associated with loss of H19 expression. Thus, imprinting of a large domain of the maternal chromosome results in a reversal to a paternal epigenotype. These data also suggest an epigenetic mechanism for inactivation of H19 as a tumour suppressor gene. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MICHIGAN, SCH MED, HOWARD HUGHES MED INST, ANN ARBOR, MI 48109 USA
2. UNIV MICHIGAN, SCH MED, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA
3. UNIV MICHIGAN, SCH MED, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA
4. CROSS CANC INST, MOLEC ONCOL PROGRAM, EDMONTON T6G 1Z2, AB CANADA
5. MARYLAND CTR HLTH STAT, BALTIMORE, MD 21201 USA
6. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA
7. JOHNS HOPKINS UNIV, SCH MED, DEPT MOLEC BIOL & GENET, BALTIMORE, MD 21205 USA
8. JOHNS HOPKINS UNIV, SCH MED, DEPT ONCOL, BALTIMORE, MD 21205 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: NU306 |
| ISSN: 1061-4036 |
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