Lay Abstract
Almost all desmoid tumors have a change (a mutation) in either a gene called CTNNB1 or less commonly the APC gene. These mutations are thought to play a major role in causing the disease and the type of mutation may determine how a patient responds to treatment. Other changes in the genetic material of the tumor have also been described. In this study, we want to understand more about desmoid tumors in pediatric patients by looking at the genetic material in the tumor in patients who are participating in the pediatric clinical trial of the gamma secretase inhibitor nirogacestat. If available, some leftover tumor tissue, either from the time of diagnosis or prior to study entry and any available tumor tissue collected while taking nirogacestat or within 30 days after the last dose, will be used for these genetic tests. We will also study whether the type of mutation or the pattern of genetic changes can predict response to the study treatment and if or how the genetics of desmoid tumors differ from adult desmoid tumors. The results from this study will be published in a peer-reviewed journal. In addition, the project will be set up in the Children’s Hospital Los Angeles data sharing platform, Childhood Cancer Knowledge Base, which is cloud based, for investigators to access the data.
Scientific Abstract
Disruptions of the Wnt/β-catenin pathway are believed to play a major role in the pathogenesis of desmoid tumors. Almost all desmoid tumors have a mutation in either CTNNB1 or less commonly the APC gene. Chromosomal aberrations have also been reported in 23-35% of desmoid tumors using array comparative genomic hybridization, karyotyping or fluorescent in-situ hybridization. With exception of CTNNB1 and APC mutations, most of the molecular characterization of desmoid tumors, including the presence or absence of chromosomal aberrations, has been in tumor tissue derived from adult patients. Limited data is available on the genomic profile of pediatric desmoid tumor. As part of the pediatric study (ARST1921) through the Children’s Oncology Group of the gamma secretase inhibitor nirogacestat in patients with unresectable, progressive desmoid tumors, we will collect blood and tumor tissue for comprehensive genomic analysis using platforms validated to detected all common alterations in desmoid tumors as well as provide an opportunity for novel discovery. We will explore correlations between mutational status and genetic signatures and outcome and response. The molecular findings will also be compared to the adult genomic data available in the literature and publicly available databases. Any leftover samples will be banked for future research. This is a rare opportunity to better understand the pathogenesis of desmoid tumors in a cohort of pediatric patients prospectively treated with a novel drug. The results from this study will be published in a peer-reviewed journal. In addition, the project will be set up in the CHLA data sharing platform, Childhood Cancer Knowledge Base, which is cloud based, for investigators to access the data.
