Brain tumors meningiomas are the most common type of tumors affecting the central nervous system, occurring around the brain or spinal cord.
Every year, approximately 25,000 Americans receive a meningioma diagnosis, making it a significant health concern.
While surgery can be an effective treatment, some cases present challenges as complete removal is not always possible. Currently, there are no chemotherapy options available for these tumors.
Understanding Meningiomas at a Genetic Level
Scientific research has made progress in identifying genetic factors responsible for approximately 80% of meningiomas. However, understanding the molecular drivers behind the remaining 20% has remained elusive.
This knowledge gap prompted Dr. Mark Youngblood, a Northwestern Medicine Neurosurgery resident and the lead author of the study, to delve into the genetic underpinnings of these tumors during his Ph.D. thesis at the Yale School of Medicine.
The Study’s Approach Dr. Youngblood and his collaborators embarked on a study that integrated genomic analyses using tumor samples from patients.
Their objective was to unravel the genetic mysteries of meningiomas that exhibited structural variations, such as chromosomal breakages, and determine how these variations influenced tumor development.
Hedgehog Signaling Pathway as a Key Player
The researchers discovered that a subset of meningiomas with structural variations experienced upregulation in the hedgehog signaling pathway.
This pathway comprises genes crucial for early development and cell differentiation. To pinpoint the cause of this upregulation, they focused on two genes, IHH and SHH, located near the structural breaks.
Enhancer Hijacking Mechanism Through advanced genomic analysis called Hi-ChIP, the team unveiled a three-dimensional understanding of DNA interactions.
They found that structural variants created novel interactions between chromosomal regions that typically do not connect. This new interaction led to increased expression of the IHH gene.
The study’s findings provide a genetic explanation for a subset of meningiomas that lacked well-defined causes previously. This breakthrough elucidates the genomic drivers behind approximately one-third of such meningiomas.
Additionally, it expands our understanding of the role of the hedgehog signaling pathway in these tumors.
Importantly, this research highlights the first instance of enhancer hijacking of hedgehog pathway ligands observed in any form of cancer.
Future Treatment Possibilities
The existence of FDA-approved drugs targeting the hedgehog signaling pathway opens doors to potential treatment options for patients with meningiomas characterized by the activation of this pathway.
Further research and clinical trials will be crucial in exploring the effectiveness of these drugs in treating such tumors.
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The research findings can be found in Nature Communications.
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