SUMMARY OF INVENTION
SMARCA4 (also known as BRG1) is a catalytic subunit of the SWI/SNF chromatin remodeling complex, which has a significant role in the regulation of gene expression. Alterations in the SWI/SNF complex, and in particular the loss of SMARCA4 expression, are well documented in a number of cancers. MSK investigators discovered that mutations in the SMARCA4 gene which reduce or eliminate SMARCA4 gene expression and/or protein levels and function are linked to certain cancers – more specifically, ovarian cancers, and in particular small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Furthermore, restoration of SMARCA4 gene expression and/or protein levels and functionality has been shown to suppress cell growth, which provides a potential avenue for therapeutic development.
SCCOHT is a rare, highly-aggressive form of ovarian cancer seen primarily in younger patients, and it has extremely low survival rates for later-stage disease when it has spread beyond the ovary. Since SCCOHT presents a difficult histological classification, the presence of a SMARCA4 mutation has started being used clinically to prognosticate risk of malignancy, confirm or exclude diagnosis of SCCOHT in a patient, and help identify appropriate treatment.
- SCOOHT currently has a very poor prognosis for later-stage disease, and this biomarker identifies patients early on to enable optimal treatment regimens from the start.
- This biomarker also lends itself to the development of therapies which restore SMARCA4 expression and/or functionality, which may include drug classes such as EZH2 and PARP inhibitors.
An estimated 24,500 women per year in the United States will be diagnosed with ovarian cancer, with a small percentage of those being SCCOHT patients facing poor prognosis. This biomarker test has started being used clinically to identify at-risk patients at an earlier stage, and it may additionally offer significant value in facilitating the development of therapeutic agents that specifically address the SMARCA4 mutation.
- Jelinic P, et al. (2014) Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nature Genetics (PubMed link)
AREAS OF APPLICATION
Diagnostic, biomarker, SMARCA4-driven ovarian cancer, SCCOHT
STAGE OF DEVELOPMENT
Ready to use
United States national application filed/published, US 15/109,403
Douglas A. Levine, MD, Former Laboratory Head at MSK