For more than a century, scientists have tried to link the tumor's origins to one of the seven different types of cells that make up the retina. Although researchers have presented evidence to support various candidates, Dyer said the answer has remained elusive. Identifying where the tumor begins would likely speed efforts to develop new chemotherapy drugs. Increasingly, such agents are designed against particular molecular pathways active in cancer cells.
For this study, researchers took a comprehensive, unbiased approach to the search that included molecular, cellular and chemical analyses of tumor cells. Dyer and his colleagues reported that retinoblastoma tumors in both humans and mice include features from several different types of cells in the retina. The list includes cells called amacrine and horizontal interneurons, retinal progenitor cells and photoreceptors.
Investigators also screened individual cells from 192 retinoblastoma tumors to gauge the activity of about 20,000 human genes and nearly 19,000 mouse genes. The tumor cells came from the 52 patient in the study, mouse models of retinoblastoma and human tumors transplanted and growing in the eyes of mice. Scientists were surprised to find evidence in those cells that genes in multiple developmental pathways were functioning, including some pathways not normally expressed simultaneously.
Screening data are now available at no cost for use by other scientists at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE29686, "The finding that normal developmental programs are completely deregulated in this tumor is surprising and unexpected. It could also have therapeutic implications," Dyer said.
Researchers found retinoblastomas in both mice and humans have remarkably similar molecular profiles. Both involved very few genetic changes that distinguished normal cells from malig
|Contact: Summer Freeman|
St. Jude Children's Research Hospital