Aim 2: Molecular profiling of tumors
Characterize the genomic and proteomic profiles of gynecologic cancers to help evaluate clinical behavior and response to treatments.
DNA is the blueprint of genetic information that encodes the proteins that compose our body. Alterations in genes can lead to abnormal proteins that cause cancer. Much of the research associated with the Gynecologic Disease Program will involve molecular profiling of different cancer tissues. We will be attempting to identify specific gene alterations and the resultant abnormal protein expressions that are associated with different types of gynecologic cancer, pre-cancerous lesions and benign tumors. Using the extensive clinical data collected from participating patients, we will be able to control for a number of confounding demographic and environmental influences.
Gynecologic cancers vary with respect to grade, histology, stage, response to treatment and survival. It is now appreciated that this clinical heterogeneity is attributable to differences in underlying molecular pathogenesis. Some cancers arise in setting of inherited mutations in a cancer susceptibility genes, but most occur sporadically in the absence of a strong hereditary predisposition. The spectrum of genes that are mutated varies between cancer types. There also is significant variety with respect to the spectrum of genetic changes within a given type of cancer. Cancers with a similar microscopic appearance may differ greatly at the molecular level. In some instances, molecular features may be predictive of clinical phenotypes such as stage, histologic type and survival.
Over the past year, our group has
demonstrated unique gene expression patterns that are associated with histology,
race, and nodal metastasis in endometrial cancers (see publications).
As we gain a more complete understanding of the clinical implications of various
genetic alterations in gynecologic cancers, the molecular profile may prove
valuable in predicting clinical behavior and response to treatment.
Investigators at WRAMC, Windber Research Institute (WRI), and the University of Pittsburgh Cancer Institute (UPCI) will identify genomic and proteomic signatures of endometrial, cervix, and ovarian cancer. Analysis of precancerous and normal tissues from the endometrium, cervix and ovary will also facilitate identification of the molecular events that are associated with the progression of gynecologic carcinogenesis. The majority of the genomics analysis (oligonucleotide array, comparative genomic hybridization array, etc) will be performed at WRAMC, while the proteomic analysis (MALD-TOF, Q-TOF, Ion Spray, etc) will be performed at WRI and UPCI (SELDI-TOF).
The data from multiple high through-put analysis will be centralized in the Data Ware House for the Gynecologic Disease program and combined with clinical and epidemiologic data. Continued growth of the Tissue and Data Acquisition Activity will facilitate targeted investigations using very select cases from the repository. Future analysis of specific tumors will also be complemented by the clinical data as well as the molecular information stored on these specimens in the Data Ware House for the Gynecologic Disease Program.