Although pediatric cancer remains relatively rare, it is the leading cause of death by disease in children past infancy. Recent studies have shown that ~10% of all children with solid tumors (in the brain or other organs) are born with a mutation in a known cancer predisposition gene, demonstrating that there is significant genetic component to cancer in children.

The Plon lab seeks to better define the genetic predisposition to childhood cancer. One recent study from our lab surveyed 615 children with rhabdomyosarcoma (RMS), a cancer that forms in muscles, to learn how often these patients were born with a mutation in cancer genes. Surprisingly, we found six patients with mutations in th...

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Although pediatric cancer remains relatively rare, it is the leading cause of death by disease in children past infancy. Recent studies have shown that ~10% of all children with solid tumors (in the brain or other organs) are born with a mutation in a known cancer predisposition gene, demonstrating that there is significant genetic component to cancer in children.

The Plon lab seeks to better define the genetic predisposition to childhood cancer. One recent study from our lab surveyed 615 children with rhabdomyosarcoma (RMS), a cancer that forms in muscles, to learn how often these patients were born with a mutation in cancer genes. Surprisingly, we found six patients with mutations in the BRCA2 gene. BRCA2 is well known causing an increased risk of cancers in adults, in particular, breast, ovarian and pancreatic cancer. The BRCA2 gene works with its partner PALB2 to play an important role in the repair of DNA damage, to prevent cancer from developing. Mutations in these genes increases the risk of cancer. Our studies and other pediatric cancer studies suggest that mutations in BRCA2 and PALB2 also increases the risk of cancer in children.

In this grant we propose to determine mutations in the BRCA2 or PALB2 genes work to cause pediatric tumors. Early data suggests that this mechanism is different from adult tumors. This work is important because there are specific medications used to treat adult tumors with BRCA2 or PALB2 mutations.

For this project, the Plon lab will be analyzing tumors from children with these mutations. They are working closely with Kyle Miller, an expert on DNA repair research at UT Austin, and Jason Yustein, an expert in modeling RMS tumors in mice at Baylor. Together this new collaborative team plan to discover how mutations in these adult-onset cancer genes can affect DNA repair and result in these pediatric cancers (with an initial focus on RMS). They will also measure how these tumor cells respond to emerging targeted therapies.

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