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2024 Post-doctoral Fellowship Grant
Shahab Sarmashgi, Recipient
The Broad Institute, Inc.
Mentor: Rameen Beroukhim
Identifying DIPG Vulnerabilities Conferred by Whole-Arm Chromosomal Alterations
It is hard to imagine a worse tumor than diffuse intrinsic pontine gliomas (DIPGs). These are aggressive brain tumors that grow in the most sensitive part of children’s brains, and are always fatal–usually within
months of diagnosis. One major reason that DIPGs are difficult to treat is that they vary from patient to patient, and even from cell to cell within a tumor. To effectively treat DIPG or any other tumor, the goal is to get rid of all the cancer cells inside it. One strategy that scientists are exploring is to focus on genetic changes that are common across all DIPG tumors. These are like the “early events” that happen in cancer development and are found in all the tumor cells. If we can target these changes, we will have a chance at removing the tumor completely. However, with DIPGs it has been hard to find these early events that could be targeted with drugs.
In DIPGs, one of the early events is changes in the number of chromosomes they harbor. Normally, healthy cells have 23 pairs of chromosomes, each with a short and long arm. But DIPGs, like most aggressive tumors, lose or gain entire chromosome arms. These changes help the tumor grow. Each of these chromosome arms can contain hundreds to over a thousand genes, and it is extremely difficult to understand the overall effects of changing them all simultaneously. We have a hypothesis: these whole-arm changes in chromosomes may create unique vulnerabilities in the tumor cells that can be targeted with new and unconventional treatments. By focusing on these shared changes, our hope is to find novel therapies that are effective against DIPGs and offer new hope to children and families affected by this devastating disease.