Genetics

U-M Cancer Center scientists are studying several genes that cause pediatric adrenal cancer and, when mutated, appear to be involved in adult cancer, as well.

One of the most important is called IGF2, insulin growth factor2. Mutations in IGF2 are found in children with adrenal cancer who have a disease called Beckwith-Wiedemann syndrome. UMCCC researchers have discovered that IGF2 is highly overactive in adult adrenal cancer cells (meaning the cells make too much IGF2 protein). This suggests IGF2 may be an important mediator or initiator of adrenal cancer. Scientists in the U-M adrenal cancer program are studying IGF2 signaling in mice to see how mutations in this gene affect stem cells in the adrenal cortex.

Two other genes under intensive study are p53 and APC. Mutations in p53 cause Li-Fraumeni syndrome in children. These children often develop adrenal cancer. The APC gene is part of the Wnt signaling pathway -- one of the most important signaling pathways involved in self-renewal of stem cells. People who inherit APC mutations have a high risk of developing colon, adrenal and other types of cancer.

If the APC gene is mutated, cells have high levels of a signaling molecule called beta-catenin. Scientists in the U-M adrenal cancer program have discovered that beta-catenin is present only in the outer membrane of the adrenal cortex - the same place where adrenal stem or progenitor cells are located. This supports the hypothesis that adrenal cancer occurs due to mutations in adrenal stem or progenitor cells.

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