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Imprinted genes in liver carcinogenesis
A T De Souza1, T Yamada, J J Mills
1Department of Safety of Medicines, Zeneca Pharmaceuticals, Macclesfield, Cheshire, United Kingdom.
Summary
Genomic imprinting affects gene expression, influencing embryogenesis and cancer. Species differences in imprinted genes, like M6P/IGF2R, impact tumor formation and human risk assessment.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Genomic imprinting results in non-biallelic gene expression, crucial for development.
- Imprinted genes, including insulin-like growth factor 2 (IGF2) and its receptor (M6P/IGF2R), are implicated in carcinogenesis.
- IGF2 promotes growth, while M6P/IGF2R inactivates IGF2 and activates TGF-beta.
Purpose of the Study:
- To investigate the role of imprinted genes in tumor formation.
- To examine the M6P/IGF2R locus in human tumors and compare imprinting patterns between species.
Main Methods:
- Analysis of the M6P/IGF2R locus (6q26-q27) in human liver and breast tumors.
- Comparison of M6P/IGF2R gene imprinting status in humans and mice.
Main Results:
- High frequency of loss of heterozygosity and mutations at the M6P/IGF2R locus in human tumors.
- M6P/IGF2R functions as a tumor suppressor.
- M6P/IGF2R is biallelically expressed in humans but monoallelically in mice.
Conclusions:
- Species-specific imprinting of M6P/IGF2R may explain differential tumor susceptibility.
- Differences in imprinted gene status are critical for human carcinogenesis risk assessment when using mouse models.