Integrated Cancer Research Center Seminar

Event Details
Contact

John McDonald, PhD

Summaries

Summary Sentence: "Recurrent Fusion Genes in Ovarian Cancer" - Laising Yen, PhD - Baylor College of Medicine

Full Summary: Georgia Tech has been a leader in the development of collaborative approaches to both cancer diagnostics and therapeutics. The mission of the Integrated Cancer Research Center (ICRC) is to facilitate integration of the diversity of technological, computational, scientific and medical expertise at Georgia Tech and partner institutions in a coordinated effort to develop improved cancer diagnostics and therapeutics.

"Recurrent Fusion Genes in Ovarian Cancer"

Laising Yen, PhD
Assistant Professor
Department of Pathology & Immunology
Department of Molecular and Cellular Biology
Baylor College of Medicine

Ovarian cancer is the fifth leading cause of cancer death in women. Almost 70% of ovarian cancer deaths are due to the high-grade serous subtype, which is typically detected only after it has metastasized. Characterization of high-grade serous cancer is further complicated by the significant heterogeneity and genome instability displayed by this cancer. Using high-throughput transcriptome sequencing of seven patient samples combined with experimental validation at DNA, RNA and protein levels, we identified several cancer-specific fusion genes. Among them, CDKN2D-WDFY2 occurs at a frequency of 20% among sixty high-grade serous cancer samples but is absent in non-cancerous ovary and fallopian tube samples. This is the most frequent recombinant event identified so far in high-grade serous cancer implying a major cellular lineage in this highly heterogeneous cancer. The parental gene, CDKN2D, is a cell-cycle modulator that is also involved in DNA repair, while WDFY2 is known to modulate AKT interactions with its substrates. Transfection of cloned fusion construct led to a gain of a short WDFY2 protein isoform that is presumably under the control of the CDKN2D promoter. The expression of short WDFY2 protein in transfected cells appears to alter the PI3K/AKT pathway that is known to play a role in oncogenesis. Thus CDKN2D-WDFY2 could very well represent a major cellular lineage important for detecting and classifying heterogenous ovarian carcinomas, and could provide insight into the underlying mechanism of this deadly disease. This is critical, given that ovarian cancer kills 140,200 women worldwide each year, and few ovarian cancer-specific molecular alterations are currently available for targeting and screening.

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Additional Information

In Campus Calendar
Yes
Groups

Parker H. Petit Institute for Bioengineering and Bioscience (IBB)

Invited Audience
Undergraduate students, Faculty/Staff, Graduate students
Categories
Seminar/Lecture/Colloquium
Keywords
IBB, ICRC Seminar
Status
  • Created By: Colly Mitchell
  • Workflow Status: Published
  • Created On: Mar 18, 2014 - 5:21am
  • Last Updated: Apr 13, 2017 - 5:22pm