Development of Tumor Specific Transcript Panels

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Human tumors have numerous genetic and
epigenetic alterations that produce complex downstream changes in the
expression levels of many genes. While some of these changes are necessary
for the maintenance of the malignant phenotype, many others are sporadic or
non-essential. One of the main challenges in new drug development for cancer
is the identification of relevant therapeutic targets among a substantial
number of these spurious background changes. Ideally, such a target would be
tumor specific, present in a majority of tumors and necessary for tumor cell
survival.

The central hypothesis in this proposal is that tumors that appear different
based on genetic changes alone, share converging downstream tumor specific
pathways.

The short-term objective of this proposal is to develop laboratory tools that
are necessary to find these convergent pathways. The long-term objective is
to validate our laboratory findings in primary human tumor samples and a broad
cell line panel.

The specific aims of the project are: 1.) Establishing a panel of human tumor
cell lines by ectopic expression of different transforming gene sets. 2.)
Identification of the mRNAs expression pattern changes common to multiple
transformation pathways and cellular backgrounds. 3.) Organization of the
individual tumor specific changes into common pathways.

The significance of this project is that the tools that are developed in the
short-term will have broad applications for all human tumor types, and in the
long-term, the results will have the potential to lead to new cancer treatment
strategies.

The experimental design will take advantage of unique tumorigenic human cell
lines expressing defined transforming genes. These cells were recently
developed by the laboratory in which these studies will be performed.
Suppression subtractive hybridization (SSH) will be used to compare cell lines
with different genetic backgrounds, in order to progressively eliminate all
the genes that are non-essential for the tumorigenic phenotype. This tumor
restricted gene panel will be used to profile primary human tumor samples.
The pre-selection process will simplify data collection and interpretation.
The priority of this project will be the development of the tumor restricted
gene panel as a tool, rather than large scale expression profiling.

The candidate, Dr. Tan A. Ince, will work at the Whitehead Institute for
Biomedical Research, under the mentorship of Dr. Robert Weinberg and with the
long-term goal of establishing an independent research career.
StatusFinished
Effective start/end date8/13/016/30/08

Funding

  • National Cancer Institute: $139,320.00
  • National Cancer Institute: $69,660.00
  • National Cancer Institute: $69,660.00
  • National Cancer Institute: $139,320.00
  • National Cancer Institute: $139,320.00
  • National Cancer Institute: $139,320.00

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