Configuration and rearrangement of the human GAGE gene clusters.

The GAGE protein is detected only in cancer and in testis and is expressed from a cluster of nearly identical gene copies on the X-chromosome. We determined the lengths of these GAGE gene clusters from human families, identical twins, and in clinical samples from cancer patients. The GAGE cluster lengths proved to be highly heterogeneous, ranging from 13 to 39 gene copies, with an average content of 20 GAGE genes per cluster. Low levels of mei-otic rearrangement in families and mitotic rearrangement in adult solid tumors are detectable. Analysis of Rothmund -Thomson syndrome (RTS) kindreds and probands showed GAGE cluster inheritance and stability indistinguishable from that found in non-RTS individuals. These observations support the concept of evolutionarily rapid rearrangement of clustered repetitive sequences in the human genome.