The goals of this hamartoma research proposal overall are to elucidate the molecular signaling pathwaysthat regulate cell size and growth responses involving the tumor suppressor genes TSC1, TSC2, LKB1, andPTEN, and to identify molecular markers and therapeutictargets. The role of this core is to provide criticallynecessary pathologic materials and pathologic expertise for the review and interpretation of translationofthese findings to human hamartoma specimens. This is critically important, because findings fromcellularand mouse model systems must be validated in human clinical specimens. Although there are severaltranslational studies of this kind reported for TSC, there is a remarkable dearth of such studies for Cowdenand Peutz-Jeghers syndromes, which correspond to germline mutation in PTEN and LKB1, respectively. Inaddition, the studies in TSC are limited in scope. Thus, this core will serve a critical role in the development and interpretation ofimmunohistochemicalstains that will confirm and extend findings from in vitro studies to human clinical specimens. This core willalso serve an important role in the review of pathology seen in the mouse models developed as part of thisprogram, and will also develop and analyze immunohistochemicalstains on rodent tumors that model variousaspects of hamartoma development. Thus, our three aims are:
Aim 1. To provide a Human Pathology Core of hamartoma lesions for analysisin collaboration with the Project investigators of this P01.
Aim 2. To develop and performimmunohistochemical studies on human hamartoma specimens, to provide clinical translation of tissueculture and mouse model findings.
Aim 3. To perform immunohistochemicalstudies on pathologyspecimens from mouse models of TSC and PJS, and derivative models to be generated in this P01 byProjects 1and 2.
Showing the most recent 10 out of 289 publications
