DeGregorio Family Foundation Supports Critical Genetic Investigation

The DeGregorio Family Foundation made a grant of $100,000 to two distinguished researchers at the Dana Farber Cancer Institute, Dr. Adam Bass and Dr. Matthew Meyerson, to conduct investigations into the genes and the genetic differences which are drivers of esophageal cancers.

In the first phase of the research, the doctors analyzed over 150 esophageal adenocarcinoma samples for recurrent genomic amplifications or deletions. Because amplified regions of tumor genomes can indicate the presence of tumor promoting genes, and deleted genomic regions may be missing key genes that block tumor formation, this type of analysis (known as copy number analysis) is a key part of building a holistic understanding of the biology underlying esophageal cancer. We then conducted similar analyses in stomach and colon cancers and compared the pattern of genomic alterations between these three categories of cancers. The doctors’ evaluation of these results provided them with insight into several of the critical genes that are potentially the keys to esophageal and gastric cancer. These include genes that can be blocked by commercially available drugs (and other drugs in clinical trials), which would provide a scientific rationale to pursue preclinical and possibly clinical studies of esophageal cancer focused on these agents.

In the second phase of our investigation, funding from the DeGregorio Family Foundation played a crucial role in initiating sequencing a set of key genes within esophageal adenocarcinoma samples, and DeGregorio initial funding to attract additional funding resources to complete the sequencing of all genes within a larger collection of samples. Drs. Bass and Meyerson are now sequencing the final samples in this group and have begun analyzing the vast data set that resulted from this work. We believe that this effort will result in very significant insights into the pathogenesis of esophageal adenocarcinoma once the analysis is complete. This work is the critical first step in the identification of potential therapeutic targets which are mutated in a number of the esophageal cancers which were studied, and this information is essential to discovery of additional novel genes that may influence cancer formation. The doctors will be writing up their data and analysis in the very near future, and publishing their findings soon thereafter. Dr. Bass and Dr. Meyerson have also begun performing pre-clinical studies based on the candidate drug target and are conducting further experiments to explore the role of the aforementioned genes.

The DeGregorio Family Foundation is thrilled by the outcomes of this research and the way in which it will have a direct impact on the work of other researchers and the ability to develop and evaluate targeted therapies. We at the foundation look forward to continuing to share news related to this early work.

DeGregorioFunded Research and Grants

The Degregorio Family Foundation is pleased to announce that we have awarded a research grant for $100,000 to:

Click to view Dr. Meyerson’s Biography

Below is a description of the winning grant.

Principal Investigator: Matthew Meyerson MD, PhD

Mutation discovery in esophageal carcinoma

Until recently, our limited understanding of the causes of esophageal and gastric cancers has held back our ability to develop new treatments for these deadly diseases. A key way in which we need to improve our knowledge of these tumors is to define the specific alterations in the DNA (or genome) of that are responsible for the development of these diseases. Beyond merely allowing us to understand these cancers, identifying the critical genetic mutations underlying esophageal and gastric cancer may elucidate new drug targets that can be quickly translated into new therapies for our patients. It is with this goal that we were fortunate to receive generous funding from the DeGregorio Family Foundation. When we made our proposal to the DeGregorio Foundation in 2009, we had the goal of looking for genetic mutations in a set of key cancer associated genes in a collection of 80 esophageal cancers. However, the technologies that are allowing us to study the cancer genome are moving and changing so quickly that by the time the grant was funded, we knew that we could do better than what we had originally proposed.

Therefore, we have worked to combine resources using funds from the DeGregorio Family Foundation with funds from the National Institutes of Health and collaborators from other cancer centers to build a more ambitious effort to understand the genetic roots of esophageal cancer. We have made great progress in two paths to understand these cancers.

First, we have completed the largest study to date of the regions of the genome that are commonly amplified or deleted in esophageal adenocarcinoma. This analysis is helping to point to new therapies that should be tested in patients with specific gene alterations. These data were presented this year at the annual American Association for Cancer Research meeting and will be submitted for publication soon.

Next, we have embarked upon an ambitious effort to sequence the DNA in a collection of esophageal cancers. This work has great potential to identify new and unforeseen genetic alterations that will inform the clinical and scientific research community on new ways to study and treat these tumors. This DeGregorio Family Foundation has been essential to our ability to do conduct this research and we are grateful for their support.

Adam Bass, MD and Matthew Meyerson, MD, PhD