Grant Details
Grant Number: |
1R03CA096447-01 Interpret this number |
Primary Investigator: |
Chen, Taiping |
Organization: |
Wood Hudson Cancer Research Lab, Inc |
Project Title: |
Tgf Beta Receptor Type 1 in Ovarian Cancer |
Fiscal Year: |
2002 |
Abstract
DESCRIPTION (provided by applicant):
TbR-I (transforming growth factor beta receptor type I) is a central
determinant of the TGF-b signaling pathway. Genetic alterations of TbR-I are
significantly high in our recent studies of ovarian cancer. We hypothesize
that diminishing of TGF-b signaling by harboring a germline deleted allele
(del(GGC)3) or somatic mutations in the TbR-I gene is associated with ovarian
tumor progression. Cancers of different organs may have different propensities
to accumulate genetic alterations of TbR-I. Understanding of the genetic
mutation profile of TbR-I in ovarian carcinoma will help to decipher the
molecular mechanisms of loss of TGF-b mediated growth inhibition. These
results may provide basis for a complex epidemiologic investigation and
translate into clinical applications such as diagnostic and prognostic
indicators for patients. In order to better understand the etiologic relevance
of genetic alterations of TbR-I in the clinical and histopathological stages
of human ovarian cancer, the applicant proposes the following Specific Aims:
l)to identify the ovarian cancer patients with germline deletion in TbR-I
gene; 2)to determine the frequency of germline deletion in non-cancer control
population; 3)to determine somatic mutations in ovarian cancer including
associated metastases.
These studies of the TbR-I gene will be performed on paraffin-embedded tissue
sections of ovarian carcinomas and non-tumor specimens. With careful tissue
microdissection and sensitive PCR-SSCP technique of analyzing a significant
number of tumors at various stages and non-tumor specimens, we will obtain
clues: 1 )whether frequent germline deletion (del(GGC)3) of TbR-I is a useful
marker to indicate high risk of ovarian cancer development and worse
prognosis; 2)whether the inactivation of TbR-I gene plays an important role in
the switch from non-invasive to invasive and metastatic cancer. The
information obtained in this project will provide a basis for the evaluation
of the genetic changes as possible indicators that distinguish patients with
highest risk of developing advanced disease. These studies may eventually lead
to better strategies for cancer prevention and intervention.
Publications
None