Meningiomas are the most common primary brain tumors. While typically of benign histology, they can be associated with significant neurological morbidity and have the potential for malignant transformation. In our previous studies, we completed genomic analysis of over 700 meningiomas using whole exome and targeted next-generation sequencing, identifying driver mutations in 12 genes and establishing mutually exclusive molecular subgroups. We now propose to investigate the molecular mechanisms underlying the formation of TRAF7-dependent meningiomas (which represent up to one quarter of all meningiomas), undertake molecular genomic analyses to identify somatic coding and non-coding or genomic events in TRAF7 tumors that progress to higher grades. We also propose to test and validate candidate drug efficacy using primary cultures from surgically resected meningiomas carrying TRAF7 aberrations, as well as mouse models of meningioma that we have established.

Public Health Relevance

Meningiomas are the most common brain tumor and are usually benign, but because they cause neurological deficits by compressing brain structures, they are treated surgically or with radiation. The proposed research is relevant to public health because understanding the genomic architecture of meningiomas will provide the necessary background to test the response of these tumors to targeted drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS110824-01A1
Application #
9887847
Study Section
Cancer Genetics Study Section (CG)
Program Officer
Fountain, Jane W
Project Start
2020-07-01
Project End
2025-04-30
Budget Start
2020-07-01
Budget End
2021-04-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520