Alex's Lemonade Stand Foundation (ALSF) presents a virtual childhood cancer lecture featuring Alex Kentsis, MD, PhD.
During this lecture, participants will:
1) Review causes of somatic mutations in developing tissues.
2) Define domesticated DNA transposases and their evolutionary origins and physiologic functions.
3) Outline current and future research to translate these insights into improved therapies for patients.
Dr. Kentsis describes his presentation:
“How do young people develop cancer? Most have not lived long enough to accumulate mutations due to aging or environmental exposure. And most do not have any apparent cancer predisposition from inheritance of cancer-causing gene mutations. Recently, my laboratory has discovered an unanticipated cause of childhood solid tumors, resulting from the aberrant activity of the PGBD5 DNA transposase that can promote rearrangements of human genes. Related mechanisms are responsible for chromosomal translocations and deletions of tumor suppressor and oncogenes induced by the RAG1/2 DNA recombinase in lymphoid leukemias and lymphomas, and unexpectedly in a large proportion of childhood myeloid leukemias.
We reason that PGBD5, RAG1/2 and other domesticated DNA transposases are normally controlled to promote development of healthy cells in early life, but become dysregulated in cells that give rise to various tumors in children and young adults. Here, I will present recent evidence for this hypothesis, and outline future studies needed to understand the causes of childhood cancers and rational strategies for their improved treatment.”
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