The goals of this hamartoma research proposal overall are to elucidate the molecular signaling pathways that regulate cell size and growth responses involving the tumor suppressor genes TSCl, TSC2, LKBI, and PTEN, and to identify molecular markers and therapeutic targets. Thus, the overall goal of this research program is to provide insight into the pathogenesis of the tumors that occur in tuberous sclerosis (TSC), Peutz-Jeghers syndrome (PJS), and the PTEN syndromes. The focus of the studies proposed in Projects 1, 2, and 3 is to improve our understanding the cellular function of the proteins encoded by these genes, through identification and characterization of phosphorylation targets, interacting proteins, and those proteins which are critical downstream or upstream elements in these pathways, and testing these hypothesis in mouse animal models.
The Specific Aims are Aim 1. To provide a pathology expertise and tissue samples for use by investigators of this P01 for the proposed studies of hamartoma tumor suppressor genes.
Aim 2. To perform immunohistochemical studies on human hamartoma and cancer specimens, to extend pathway connections from tissue culture and mouse model studies.
Aim 3. To study renal cell carcinomas related to TSC patients and TSC1/2 genes. TSC patients are known to have increased risk of developing renal cell carcinoma. We will perform whole genome exon squencing of these tumor samples.

Public Health Relevance

The role of this core is to provide critically necessary pathologic materials and pathologic expertise for the review and interpretation of translation of molecular findings discovered by the Projects to human tumor specimens, including hamartoma tumors and human cancers. This is critically important, because findings from cellular and mouse model systems must be validated in human clinical specimens.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA120964-08
Application #
8719038
Study Section
Special Emphasis Panel (ZCA1-RPRB-O)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
8
Fiscal Year
2014
Total Cost
$140,452
Indirect Cost
$9,781
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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