The SWI/SNF (or SWItch/Sucrose Non-Fermentable or BAF) complex plays an important role in cancer biology

genomics of aberrant swi/snf cancers

Since The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET), alterations in the SWI/SNF complex have been found in many cancers. More recent work from https://genie.cbioportal.org/ which brings together the experience from a number of institutions have identified numerous cancers with changes in the SWI/SNF complex.

We are focused on SMARCB1. This gene is deleted and altered in cancers with some of the poorest outcomes such as:

• rhabdoid tumor (kidney)

• renal medullary carcinoma (kidney)

• atypical teratoid rhabdoid tumor (ATRT, brain)

• epitheloid sarcoma (soft tissue, muscle)

We continue to collaborate with the Children’s Oncology Group, Susan Chi, Jaclyn Biegel and Matt Young to find new genomic insights in this group of cancers.

New therapeutic strategies

We are using high throughput functional genomics to identify new therapeutic targets and in conjunction with next-generation patient derived models, we are validating and identifying mechanisms behind these targets in vitro and in vivo.

We will use mono- and multi-therapeutic strategies to help develop rational clinical trials either locally with James Fangusaro and Thomas Cash (at Aflac Cancer and Blood Disorders Center), Joanna Yi (at Texas Children’s Hospital) and Sue Chi, Steve Dubois and Elizabeth Mullen (at Dana-Farber Cancer Institute) or nationally with the Renal Tumors Committee at the Children’s Oncology Group.

structure and function of smarcb1

Recent studies have begun to elucidate the structure of the SWI/SNF complex and interactions of SMARCB1. This large complex is a chromatin remodeling complex that has a number of roles in cell function.

Working with Sue Chi (at Dana-Farber Cancer Institute) and Jaclyn Biegel (at Children’s Hospital of LA), we are studying the function of variants of SMARCB1.