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Circulating microRNA signatures among BRCA1/2 mutation carriers
Using prior funding from Tina’s Wish, we have developed a blood-based screening test for ovarian cancer that relies on serum levels of microRNA (miRNA), small pieces of genetic material secreted by cancer cells. The test is now being validated in the MiDe Study, a nationwide clinical trial for women at high risk for ovarian cancer, primarily those with mutations in the genes BRCA1 and BRCA2. However, these genetic mutations do not confer equal risk of ovarian cancer, nor do we understand how specific changes in miRNAs relate to individual genetic factors. In the current study, our first aim is to examine how BRCA1 and BRCA2 mutations differ with respect to circulating miRNA profiles, which will be essential for interpreting a miRNA-based screening test within the context of an individualized cancer risk assessment. By examining 1,212 samples from 987 patients pulled together from three countries, we will provide the most comprehensive analysis to date of the relationship between BRCA mutations and miRNA expression. Our second aim is to understand why these miRNA changes occur. To do so, we will use laboratory models to examine the cellular mechanisms by which these specific genetic mutations induce miRNA changes and study roles for these altered miRNAs in impacting DNA repair. The combined results will be a dynamic miRNA-based screening assay that can be tailored to personal risk of ovarian cancer and that is informed by the biological changes that drive this disease.
To learn more about Dr. Chowdhury’s and Dr. Elias’ work, click here. The MiDe Study (MicroRNA Detection Study) website is now live and enrolling participants at high-risk of ovarian cancer.
Dana-Farber Cancer Institute Winter 2019 Impact Newsletter: DR. DIPANJAN CHOWDHURY RECEIVES ADDITIONAL FUNDING FROM A GENEROUS DANA-FARBER DONOR
Dana-Farber Cancer Institute: NEW BLOOD TEST DEVELOPED TO DIAGNOSE OVARIAN CANCER
eLIFE, October 31, 2017 (FULL STUDY): Diagnostic potential for a serum miRNA neural network for detection of ovarian cancer
Q&A WITH DIPANJAN CHOWDHURY, PhD
Q: What is your daily routine like?
A: Over the years my daily routine has changed dramatically. As a Phd student, I was conducting experiments at the bench. Now my primary job is make sure I recruit the best people to conduct experiments, identify the best projects, provide ideas and resources. I miss being at the bench sometimes because one of the most exciting parts about a scientific career is making the first groundbreaking observation.
Q: Did you choose ovarian cancer or did it choose you?
A: The reason is very scientific. Ovarian cancer, in my opinion, is a DNA repair disease and my lab primarily focuses on DNA repair. Based on sequencing data that has come out in the last 5 years, over 50% of ovarian cancer tumors have a defect in their DNA repair machinery. That is a higher percentage than any other cancer tumor types we know of. I started out looking at the more basic biology around DNA repair but as I began to ask “why is this important?” the first thing that came to mind was ovarian cancer.
Q: What are your short-term and long-term visions or hopes for the future in relation to science and ovarian cancer research?
A: The biggest issue with ovarian cancer is the lack of an early detection screen. My short-term goal is to come up with a strong and powerful body of biomarkers that can be part of a regular physical. Ideally, a noninvasive and affordable test – similar to how we have been able to control heart disease due to high cholesterol. An early detection mechanism would significantly lower the fatality rate of this disease.
Q: In your opinion, how is Tina’s Wish different from other organizations?
A: Tina’s wish is unique in its focus. Foundations with a non-specific approach sometimes get diluted. A strong effort in early detection makes Tina’s Wish stand out. I particularly like this about the foundation because it makes it easier to work with the other grantees. Everyone has the same common vision. It helps to have people in the room that are focused on one very specific goal.
Q: What is your perspective on the future of scientific research?
As scientists of this generation, we need to inspire our youth to take an interest in science, conduct research and think about solving complex problems. There is a lot to be done in the cancer research field. We are still in the early days and cancer is an epidemic. Almost every person in the world has been affected by cancer or knows someone who has been affected by cancer. As a community, we need to fight cancer in different ways and inspire the younger generation to join the battle.