Rare Tumor Research

Advances in genomic technology have ushered in a new age of cancer research with countless examples of fascinating discoveries and breakthrough treatments. We have recently discovered universal SMARCA4 mutations that appear to be a critical driver for a very aggressive tumor that affects young women — small cell carcinoma of the ovary, hypercalcemic type (PMID: 24658004).  We subsequently determined that SMARCA2 is also lost in all of these tumors (PMID: 26564006).  Both of these observations have led to improved diagnostic accuracy for this disease, in which histologic mimics are common. However, in most other solid tumors with SWI/SNF loss, a compensatory mechanistic upregulation of other complex members counteracts the functional loss of any single component. We continue to investigate the remarkable concurrent loss of both catalytic ATPase subunits to better understand this disease pathogenesis.

We also have active programs exploring other rare tumors such as uterine carcinosarcomas, uterine leiomyosarcomas, ovarian germ cell tumors, ovarian mucinous carcinomas, and low-grade serous ovarian carcinomas. For these other tumor types, we are investigating mutational burden, traditional gene expression profiles, and epithelial-mesenchymal transition. Using integrated approaches, we are able to identify essential dependencies in these rare tumors types through a comprehensive interrogation of a limited number of biospecimens. We are grateful to the many donors who help to make our initial studies into rare tumors possible so that we can generate sufficient preliminary data to compete for more traditional funding mechanisms.