A Molecular Mechanism for the Activation of Mutant TERT by the BRAF V600E/MAP Kinase Pathway

Unmet Need
The oncogenic duet of BRAF V600E and TERT promoter mutations occurs in approximately 7-8% of papillary thyroid cancer (PTC) cases and 20-50% of melanoma cases. These percentages also correspond to the proportion of cases with the poorest clinical and pathological outcomes. When mutations in either of these oncogenes alone are present, only a modest effect is observed. However, when promoter mutations are found in both oncogenes, more aggressive disease phenotypes, tumor development/recurrence, and increased mortality result. The underlying mechanism cooperatively linking these two oncogenes is unknown. Determining the molecular mechanism would have important cancer biological and clinical implications and would reveal new options to improve treatment for more aggressive forms of cancer.
Technology Overview
Johns Hopkins researchers have identified a novel molecular mechanism that describes the synergetic relationship between the promoter mutations of the oncogenes, BRAF V600E and TERT, in which the GAPBPB transcription factor, FOS, functionally bridges the two. This mechanism explains how these oncogenes cooperatively promote aggressive cancer behavior, tumor development, and disease specific mortality.
 
Stage of Development
The inventors have identified a novel molecular mechanism that explains the recently observed robust role of the genetic duet of BRAF V600E and TERT promoter mutations in cooperatively promoting the aggressiveness and poor clinical outcomes of several human cancers, thus exposing important cancer biological and clinical implications for aggressive melanoma, PTC, and other cancers.
 
Publications/Related JHU Technologies

1. Nat Commun. 2018 Feb 8;9(1):579.
2. JHU Ref. C12422 - TERT Promoter Mutations in Thyroid Cancer
3. JHU Ref. C12971 - BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer with Highest Recurrence

 
 
 
 

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