Available Technology

TRRAP and GRIN2A Mutations for the Diagnosis and Treatment of Melanoma

Using whole-exome sequencing of matched normal and metastatic tumor DNAs, researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations, many of which have not previously been known to be genetically altered in tumors or linked to melanoma. In particular, the researchers identified a recurrent “hotspot” mutation in the transformation/transcription domain-associated protein (TRRAP) gene, found the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene as a highly mutated in melanoma, and have shown that the majority of melanoma tumors have alterations in genes encoding members of the glutamate signaling pathway. Therefore, this technology not only provides a comprehensive map of genetic alterations in melanoma, but has important diagnostic and therapeutic applications. Mutations in the TRRAP and GRIN2A genes can be used as diagnostic markers for melanoma and may serve as therapeutic targets in the treatment of melanoma. In addition, glutamate antagonists have previously been shown to inhibit proliferation of human tumor cells, and therefore further investigation of the pathway in melanoma could allow for the identification of new therapeutic proteins that target this pathway.
Patent Abstract: 
Using whole-exome sequencing of matched normal and metastatic tumor DNAs, researchers at the NIH have identified several novel somatic (e.g., tumor-specific) alterations, many of which have not previously been known to be genetically altered in tumors or linked to melanoma. In particular, the researchers identified a recurrent “hotspot” mutation in the transformation/transcription domain-associated protein (TRRAP) gene, found the glutamate receptor ionotropic N-methyl D-aspartate 2A (GRIN2A) gene as a highly mutated in melanoma, and have shown that the majority of melanoma tumors have alterations in genes encoding members of the glutamate signaling pathway. Therefore, this technology not only provides a comprehensive map of genetic alterations in melanoma, but has important diagnostic and therapeutic applications. Mutations in the TRRAP and GRIN2A genes can be used as diagnostic markers for melanoma and may serve as therapeutic targets in the treatment of melanoma. In addition, glutamate antagonists have previously been shown to inhibit proliferation of human tumor cells, and therefore further investigation of the pathway in melanoma could allow for the identification of new therapeutic proteins that target this pathway.
Benefits 
Complete analysis of melanoma exome alterations. -TRRAP, GRIN2A, and the other identified mutations are highly frequent and/or highly mutated in melanomas. -Glutamate antagonists have already been shown to inhibit tumor growth. Thus, this technology may prove useful for the development of novel diagnostic tests and therapeutics.
applications 
Inventors: 
Yardena Samuels
Patent Number: 
PCT/US2012/022687 US Application No. 13/982,392 Re
Internal Laboratory Ref #: 
E-013-2011/0
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