| | |  | | | | Record from Web of Science® | | | | | | |
| RELAXATION OF IMPRINTED GENES IN HUMAN CANCER |
|
|
| Author(s): RAINIER S, JOHNSON LA, DOBRY CJ, PING AJ, GRUNDY PE, FEINBERG AP |
| Source: NATURE Volume: 362 Issue: 6422 Pages: 747-749 Published: APR 22 1993 |
| Times Cited: 605 References: 39 |
| Abstract: GENOMIC imprinting, or parental allele-specific expression of genes, has been demonstrated at the molecular level in insects and mice1,2 but not in man. Imprinting as a potential mechanism of human disease is suggested by paternal uniparental disomy of 11p15 in Beckwith-Wiedemann syndrome3 and by maternal uniparental disomy of 15q11-12 in Prader-Willi syndrome4. Beckwith-Wiedemann syndrome is characterized by multiorgan overgrowth and predisposition to embryonal tumours such as Wilms' tumour of the kidneys. A loss of heterozygosity of 11p15 is also frequently found in a wide variety of tumours, including Wilms' tumour and lung, bladder, ovarian, liver and breast cancers6-11; 11p15 also directly suppresses tumour growth in vitro 12 . Two genes in this band, H19 and insulin-like growth factor-11 (IGF2) undergo reciprocal imprinting in the mouse., with maternal expression of H19 (ref. 13) and paternal expression of IGF2 (ref. 14). Here we find that both of these genes show monoallelic expression in human tissues and, as in mouse, H19 is expressed from the maternal allele and IGF2 from the paternal allele. In contrast, 69% of Wilms' tumours not undergoing loss of heterozygosity at 11p showed biallelic expression of one or both genes, suggesting that relaxation or loss of imprinting could represent a new epigenetic mutational mechanism in carcinogenesis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV MICHIGAN, SCH MED, HOWARD HUGHES MED INST, 4520 MSRB 1, 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, DEPT PEDIAT, EDMONTON T6G 1Z2, ALBERTA CANADA
5. UNIV ALBERTA, EDMONTON T6G 1Z2, AB CANADA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: KY450 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |