Characterization of Telomere Maintenance in Tumor Models of Dyskeratosis Congenita
by Dr. Judy Wong
Our amazing 2020 Team Telomere Million Dollar Bike Ride Grant Awardee was Dr. Judy Wong! Her project, “Characterization of Telomere Maintenance in Tumor Models of Dyskeratosis Congenita”, worked to understand how cancer develops in individuals with Telomere Biology Disorders and Dyskeratosis Congenita (DC).

Currently, Dr. Wong is hoping to expand her work to understand how cancer forms in people with DC due to pathogenic variants (i.e. mutations) in the DKC1 gene. Through this research, she and her research partners hope to advance our understanding of cancer development and telomere biology and to discover new avenues for treatments for patients with DC.

In the following statement, Dr. Wong explains the importance of her research and how integral our community is to driving this work forward:

X-DC patients have an increased risk of developing cancers from blood and other origins, a direct consequence of damaged telomeres not being repaired. Paradoxically, optimal telomere maintenance is crucial for cancer growth, and X-DC tumors must overcome its telomere repair deficiency for continued cancer growth. With funding from the Million Dollar Bike Ride award, our group created X-DC tumor cells in the laboratory using patient materials from the Inherited Bone Marrow Failure Syndrome (IBMFS) cohort collected by our clinical collaborators at the National Cancer Institutes at the NIH. We discovered that X-DC tumor cells can repair their telomeres effectively, overcoming their telomerase genetic defects.

In the next phase of our project, we aim to deduce how telomerase genetic defects are overcame and would these genetic defects impact therapeutic responses of DC cancers. We will conduct experiments such as synthetic dosage lethality screens to identify unique vulnerabilities in DC tumor cells compared with their telomerase-wildtype counterparts. Our in vitro findings will be confirmed with primary tumor samples now being collected as the Team Telomere/IBMFS cohort. Data from our functional genetic screens will inform the development of targeted therapeutics, and selected targets will be characterized for their utility against DC tumors.

You are invited to participate in this study if you are:

–      In the NCI IBMFS study cohort (ClinicalTrials.gov Identifier: NCT00027274) or are willing to enroll in this study AND
–      An individual diagnosed with DC due to DKC1 AND
–      Are having a biopsy or surgery for a suspected or confirmed cancer

As part of this study, the study team at the NCI will work with your care team to obtain a sample of this biopsy or cancer for further research.

If you have questions regarding this study or believe that you may be eligible for this study (either at this time or at a future time point), please contact the NCI study team at 1-800-518-8474 or email Dr. Neelam Giri (girin@mail.nih.gov) or Dr. Sharon Savage (savagesh@mail.nih.gov).