Research Studies with DNA/Tissue Bank Samples


Cavernous angioma lesion tissue is an extremely valuable resource for researchers. Accessibility to this tissue allows for studies to move beyond mouse models and cell culture experiments, to directly investigate the genetics and biology of the human condition. An underlying theme in Cavernous angioma research is to determine all of the factors affecting lesion formation, growth, and the resulting clinical behavior. The following are examples of the ways in which researchers are currently using tissue donated to the Angioma Alliance DNA/Tissue Bank.


Investigation of the molecular mechanism underlying the development of Cavernous Angiomas

Researchers have determined that a mutation of one of three CCM (cerebral cavernous malformations) genes results in the onset of familial cavernous angioma. What remains unclear, (and is a major research focus), is the normal function if these genes. Why, when mutated, do they cause angiomas? And, are there other genes and/or proteins that are affected by such mutations and as a result contribute to lesion development? By investigating the molecular components of lesion tissue, researchers are able to address these questions.   


Investigation of genetic mechanism for the development of Cavernous Angiomas

Single cavernous angiomas can develop sporadically, but the risk of developing multiple angiomas can also be inherited by mutation in one of three CCM genes. The presence of single lesions in sporadic cases and multiple lesions in inherited cases has led to the hypothesis that lesion formation follows the Knudson two-hit mechanism. The two-hit mechanism occurs when a person has one inherited mutation in a CCM gene and then acquires another mutation in specific cells—resulting in loss of both functional copies of the gene. Researchers hypothesize that acquiring the second mutation is necessary for lesion formation and are testing the hypothesis by analyzing human CCM lesion tissue for the presence of two mutations. 


Investigation of factors contributing to clinically aggressive Cavernous Angiomas

In addition to the genetic and molecular mechanisms directly affecting cavernous angioma lesion development and growth; other factors may contribute to specific lesion behavior. Additional studies aim to characterize the immune response associated with cavernous angioma lesions. These studies investigate the relationship of antibodies and inflammation on lesions with and without aggressive clinical behavior.       


All of these studies are designed to enrich the knowledge of basic lesion biology and behavior to enable the development of a specific and non-invasive treatment for Cavernous Angioma.



webpage updated 11.5.9