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One gene helps drive growth in two childhood brain tumor groups that lack targeted therapies

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One gene helps drive growth in two childhood brain tumor groups that lack targeted therapies

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Targeting KDM2B or downstream protein complexes it recruits may exploit a vulnerability in high-risk medulloblastoma subgroups that currently lack targeted therapies, according to a study led by St. Jude Children's Research Hospital and Hopp Children's Cancer Center Heidelberg (KiTZ). The researchers found that Group 3 and Group 4 medulloblastomas depend on the protein KDM2B for growth and that removing it slowed tumor growth in preclinical models. The findings are published today in Nature Genetics.

Medulloblastoma is one of the most common malignant brain tumors in children and comprises four major subgroups. Group 3 and Group 4 medulloblastomas are high-risk subgroups that lack targeted therapies. As a result, these tumors often require intensive treatments that can cause substantial long-term side effects, underscoring the need for more precise therapeutic approaches.

Although epigenetic deregulation that disrupts normal brain development is believed to drive medulloblastoma formation, the underlying mechanisms remain incompletely understood. To better understand those mechanisms and identify vulnerabilities, St. Jude and KiTZ researchers comprehensively characterized histone post-translational modifications in patient samples from every subgroup. Changes to these modifications can affect gene expression without changing DNA sequences.

The researchers then looked for genes that regulate those histone modifications. They discovered that KDM2B, an epigenetic regulator highly expressed in Group 3 and Group 4 tumors, is essential for tumor growth. Removing the gene for KDM2B or degrading the protein suppressed tumor growth and prolonged survival in preclinical models.


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