• Alex Kentsis

  • Mar 12, 2017

Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in solid tumors

While some human cancers occur as a result of age-dependent accumulation of genetic mutations, and others are caused by deficiencies in DNA replication or repair, the causes of many oncogenic mutations remain poorly understood.

This conundrum is particularly true for solid tumors of children and young adults, as emphasized by their recent genome surveys, revealing a relative paucity of canonical tumorigenic gene mutations.

Our current research now implicates the PGBD5 DNA transposase as an oncogenic mutator responsible for site-specific mutations in rhabdoid tumors, a lethal childhood cancer.

This activity and its expression in distinct human cancers provides a plausible mechanism for site-specific DNA rearrangements in childhood and adult solid tumors. Current work is focused on defining PGBD5 tumorigenic mechanisms in solid tumors, identifying targets for rational therapy, and investigating the relationship between its physiologic functions and disease.