Elucidate the role of the MEN1 gene in carcinoid tumors and determine a functional connection between the genes MEN1, Rbp2 and p27

Matthew Meyerson, MD, PhD

Year: 2006
Institution: Dana-Farber Cancer Institute
Country: United States
State: MA
Award Type: NETRF GRANTS 2005-2017
NET Type: Gastrointestinal
Science Type: Basic


Senapati is researching whether defects in the ATRX and DAXX genes activate certain sequences in DNA that cause pancreatic NETs to form. She is also studying changes in DNA methylation to find elements that may be activated in the formation of tumors. 

What question will you try to answer through your research?

My study will address which genetic components, called retrotransposons, are expressed in pancreatic NETs (PNETs) that have mutations in the ATRX and DAXX genes, and whether an abnormal expression of retrotransposon proteins can help predict outcomes for patients. My team and I will also explore how the ATRX/DAXX mutation in PNETs leads to dysregulation of retrotransposons that are silenced and tightly regulated in normal cells.

Why is this important?

ATRX/DAXX mutations in PNETs are associated with a worse prognosis for patients. If we better understand which retrotransposons are abnormally regulated in PNETs and how they lead to cancer progression, we may be able to identify markers that may affect prognosis and develop new treatment strategies for PNETs.

What will you do as part of this research project?

We will analyze the abnormal genomes of PNETs and the aberrant regulation of their genetic components that contribute to the formation of PNETs. We will explore the role and contribution of the ATRX and DAXX genetic mutations in causing pancreatic NETs. 

How might your research improve the treatment of NETs?

This study will help us identify genes and genetic pathways that may be used to develop diagnostic or prognostic markers and immunotherapeutic strategies to target PNETs. 

What is your next step?

Our study will explore whether the expression of retrotransposon proteins is associated with poorer clinical outcomes. The results may point to possible therapeutic strategies that target these proteins in PNETs.