Dr. van de Rijn has started to perform gene expression profiling (determining at which level each of >20,000 human genes is expressed) on archival tissue of desmoid tumors, scars from desmoid patients and a large number of fibroblastic lesions using an approach developed in his laboratory. The current proposal is a logical and necessary continuation of this project. This project will use cutting edge next generation sequencing to pursue two major clinical problems in desmoid tumors. First, it is well known that not all desmoid tumors behave in the same manner. Some are very aggressive, others have an indolent behavior. While attempts have been made to develop predictors for the behavior of desmoids, these rely only on clinical parameters such as tumor size, site and age of the patient and no molecular markers for recurrence risk have been identified. At this moment it is impossible to tell with certainty which tumors require aggressive treatment and which can be followed by “watchful waiting”. Through the ability to perform next generation sequencing on paraffin embedded tumor samples he can now perform a very broad search for changes in DNA that can help predict the behavior of desmoids. The data acquired under this proposal will complement the already existing dataset in his laboratory. Through collaboration with the oncology group at Stanford and at the Dana Farber Cancer Institute, there will be access to a more than sufficient number of cases for the study. In addition to identifying markers that can be used to predict the behavior of desmoid tumors, Dr. van de Rijn will also perform an in-depth search for markers that can be used by pathologists to distinguish scar from desmoid recurrence.