Understanding the role of SMARCD1(BAF60A) in malignant rhabdoid

Trustees of Dartmouth College, Lebanon, NH

SWI/SNF chromatin remodeling complexes are groups of proteins with numerous roles in the organization and activation of DNA. These complexes are vital to the health and development of our cells, and disruption of their activity can lead to a range of diseases. Nearly 20% of all human cancers are thought to arise from mutations in the compositional subunits of SWI/SNF complexes. Malignant rhabdoid tumors (RTs) and atypical teratoid rhabdoid tumors (ATRT) are aggressive forms of pediatric cancer that typically stem from inactivating mutations in a prominent SWI/SNF chromatin remodeling complex subunit known as SMARCB1. It is widely accepted that SMARCB1 acts as a tumor suppressor when functional, but less clear how mutations in the subunit might fuel the growth of cancer cells. Unearthing the molecular mechanisms that are responsible for tumor growth in SMARCB1-mutant cancers could yield new therapies for patients suffering from rhabdoid tumors. We hypothesize that one subunit in particular, SMARCD1, is essential for maintaining the functionality of the residual complex. Further characterizing this interaction could open doors to cancer treatments targeting the residual complex via SMARCD1. We hope to identify the specific genes or features of the genome that SMARCD1 and the residual complex are targeting in cancer cells, with the ultimate goal of finding new ways to eliminate these tumors and generate better treatments for this pediatric cancer.