Our Goal:

To determine the identity of all genes of cancers that are expressed differently from normal tissues, whether the expression is increased or decreased

How Are We Doing This?

High through-put array technology allows us to directly observe and in the RNA transcript levels of each gene.

Methods

Diagnosis. The collection of genes that are significantly over- or under-expressed in cancer define a profile. These profiles are likely different for different grades and stages of disease. When one of these profiles is observed for a biopsy or other potentially diagnostic specimen, a molecular-based diagnosis including information about likely grade and other signs of aggression may be made.

Prognosis. We hope to define the profile characteristic of indolent or aggressive behavior. Biopsies that reveal one of these profiles would provide invaluable information to patients about the future behavior of their disease.

Experimental Protocol

Surgical prostatectomy specimens of consenting patients are express-delivered to the hospital pathology group.

Tumor tissue that is excess to diagnostic needs is provided for the study. The tumor tissue is frozen in liquid nitrogen within one to two hours of excision.

Investigators at SKCC and UCSD remove tumor cells by laser capture microdissection and prepare RNA or DNA.

The RNA is used for “expression analysis” on Affymetrix “chips” or microarrays fabricated at SKCC. These arrays sample the expression of over 40,000 human genes.

The DNA is used for “methylation profile” determination. Methylated genes have greatly decreased expression and methylation is altered in cancer. Methylation profiles will be determined at the Ludwig Institute and SKCC.

Dr. D. Masys working with the UCSD Super Computer will analyze the data. Clinical parameters (tissue grade, stage, patient characteristic, etc.) will be entered into the analysis.

The analysis will aim to identify those genes whose expression correlates with grade, stage, and other features. In new cases of prostate cancer, these molecular profiles would be a new guide to diagnosis and prognosis of the disease.