FRS2 Is an Oncogene in High Grade Ovarian Cancer

Abstract

Ovarian cancer is the most common cause of gynecologic cancer death in the United States. Despite aggressive surgical cytoreduction and chemotherapy, ovarian cancer remains one of the most lethal cancer types due to advanced stages at diagnosis and lack of effective systemic therapy. High-grade serous ovarian cancers (HGSOC) are characterized by widespread recurrent regions of copy number gain and loss. Here we interrogated 50 genes that are recurrently amplified in HGSOC and essential for cancer proliferation and survival in ovarian cancer cell lines. FRS2 is one of the 50 genes located on chromosomal region 12q15 that is focally amplified in 12.5% of HGSOC. We found that FRS2 amplified cancer cell lines are dependent on FRS2 expression. Furthermore, FRS2 overexpression in immortalized human cell lines conferred the ability to grow in an anchorage independent manner and as tumors in immunodeficient mice. An adaptor protein in the FGFR pathway, FRS2 induces downstream activation of Ras-MAPK pathway. These observations identify FRS2 as an oncogene in a subset of HGSOC that harbor FRS2 amplifications and a potential therapeutic target.