Defects in DNA Imprinting Affect Development and Progression of Childhood Osteosarcoma

Defects in DNA Imprinting Affect Development and Progression of Childhood Osteosarcoma
Defects in DNA Imprinting Affect Development and Progression of Childhood Osteosarcoma

Osteosarcoma in children may be impacted by a defect in DNA imprinting that also occurs in their biological parents. This new research was reported in Oncotarget.1 These imprinting defects may be predictive of survival outcomes.

The aggressive bone cancer known as osteosarcoma has a 5-year survival rate of approximately 70%, according to background information in the article. Genetic imprinting of DNA describes the situation when only 1 of 2 inherited copies of a gene is active, while the other is present but inactive. This occurs because of epigenetic inheritance through DNA methylation.

This study examined if specific gene and microRNA expression changes associated with osteosarcoma could be due to epigenetic alterations, and if these alterations are also present in a parent. The researchers examined DNA from a specific genomic location in both patients with osteosarcoma and their parents. They also used mouse models of osteosarcoma to observed imprinting defects.

The research team, led by Jingmin Shu, PhD, of the Masonic Cancer Center of the University of Minnesota in Minneapolis, found that imprinting defects are associated with the pathogenesis of osteosarcoma. These defects occur in the DNA from affected children and their biological parents.

"Through these initial studies, we found the imprinting defects as possible mechanisms altering gene and microRNA expression which are associated with osteosarcoma pathobiology," said Subbaya Subramanian, PhD, also of the University of Minnesota. "This also allows us to think imprinting defects may be a cause for osteosarcoma to develop predominantly as a pediatric cancer."

These findings set the stage for clinical investigations of drugs that modify the DNA and chromatin, explained Subramanian. In addition, genome editing tools may have a role in rectifying the imprinting defects. He stated that a larger cohort study and further investigations are needed.

REFERENCE

1. Shu J, Li L, Sarver AE, et al. Imprinting defects at human 14q32 locus alters gene expression and is associated with the pathobiology of osteosarcoma [published online ahead of print January 21, 2016]. Oncotarget. doi:10.18632/oncotarget.6965.

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