Describe how disruption of imprinting cancontribute to cancer, using the example of the H19/Igf2 cluster (maximum 200 words). In your answerinclude the following points:Describe the methylationpattern of the paternal allele and how this determines Igf2 expression statusDescribe the methylationpattern of the maternal allele and how this determines Igf2 expression statusDescribe how imprintingat the H19/Igf2 cluster is disrupted in Wilm’s tumourExplain how disruptingimprinting at the H19/Igf2 cluster contributes to cancer.
Question
Describe how disruption of imprinting cancontribute to cancer, using the example of the H19/Igf2 cluster (maximum 200 words). In your answerinclude the following points:Describe the methylationpattern of the paternal allele and how this determines Igf2 expression statusDescribe the methylationpattern of the maternal allele and how this determines Igf2 expression statusDescribe how imprintingat the H19/Igf2 cluster is disrupted in Wilm’s tumourExplain how disruptingimprinting at the H19/Igf2 cluster contributes to cancer.
Solution
Imprinting at the H19/Igf2 cluster involves differential methylation patterns on the paternal and maternal alleles. The paternal allele is methylated, silencing the H19 gene and allowing Igf2 expression. Conversely, the maternal allele is unmethylated, enabling H19 expression and inhibiting Igf2.
In Wilms' tumor, this imprinting is disrupted. The maternal allele may become methylated, silencing H19 and permitting Igf2 expression. This leads to an overexpression of Igf2, a growth factor, which can stimulate uncontrolled cell proliferation, a hallmark of cancer.
Alternatively, loss of imprinting can occur on the paternal allele, leading to activation of the normally silent H19 gene. H19 encodes a non-coding RNA that can function as a tumor suppressor, so its overexpression can also contribute to cancer development.
Thus, disruption of imprinting at the H19/Igf2 cluster, whether by changes in methylation status or loss of imprinting, can contribute to cancer by altering the expression of genes that regulate cell growth and division.
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