Movement of Genes in Nucleus May Someday Aid Diagnosis

Abstract

Listen

Translate article

When researchers realized a decade ago that genes inhabit a specific space within a cell’s nucleus and that they sometimes change location during differentiation and in certain diseases, they began to contemplate why. Tom Misteli, Ph.D., and his group at the National Cancer Institute are now asking whether they can exploit evidence of gene movement as a diagnostic tool. In a preliminary study comparing 14 invasive breast cancer tissue samples with 11 healthy breast tissue samples, the researchers found that several genes have a different physical position in the nucleus in invasive breast cancer. One gene, HES5, known to affect pathways involved in cancer, allowed identifi cation of invasive breast cancer in more than 90% of cases. The fi ndings were published in the December 14, 2009, Journal of Cell Biology . Today pathologists look through a microscope in search of distinctive changes in shape and size of the cell nucleus as signs of cancer. But the Misteli group’s approach is different because it’s quantitative and spatial. They use fl uorescence in situ hybridization to label specifi c genes in an intact nucleus. Using little tissue, just 100 – 200 cells, they can compare gene position in biopsy tissue against a standardized normal. “To the best of my knowledge, we are the only group trying to utilize the position of genes for diagnostic purposes,” said Karen Meaburn, Ph.D., in Misteli’s lab in NCI’s Center for Cancer Research. The approach makes sense to Mark T. Groudine, M.D., Ph.D., who studies gene positioning during differentiation of hematopoietic stem cells, which shifts as the precursor cells become red blood cells or white blood cells. “This may be a simple way of trying to determine if cells are normal or cancerous based on the positioning of chromosomes or genes,” says Groudine, deputy director of the Fred Hutchinson Cancer Research Center in Seattle. “It’s a very nice model.” “What’s so exciting about Karen’s paper is it’s a large number of genes and she did it in tumor biopsies,” says Joanna M. Bridger, Ph.D., deputy director of the Centre for Cell and Chromosome Biology at Brunel University in West London. “The data are so nice that she can make that correlation with diagnosis.” Meaburn did her doctoral studies in Bridger’s lab.