title: The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer.
abstract: 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, and that FRS2 overexpression in immortalized human cell lines conferred the ability to grow in an anchorage-independent manner and as tumors in immunodeficient mice. FRS2, an adaptor protein in the FGFR pathway, induces downstream activation of the Ras-MAPK pathway. These observations identify FRS2 as an oncogene in a subset of HGSOC that harbor FRS2 amplifications.
  
  
  CONCLUSIONS
  These studies identify FRS2 as an amplified oncogene in a subset of HGSOC. FRS2 expression is essential to ovarian cancer cells that harbor 12q15 amplification.
authors.affiliation: Health Sciences and Technology Program, Harvard Medical School, Boston, Massachusetts. Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Leo Y
authors.initials: LY
authors.lastname: Luo
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Eejung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Hiu Wing
authors.initials: HW
authors.lastname: Cheung
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Weir
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Dunn
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Astellas Pharma U.S. Inc., Santa Monica, California.
authors.forename: Rhine R
authors.initials: RR
authors.lastname: Shen
authors.affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts. Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. William_Hahn@dfci.harvard.edu.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C106534:FRS2 protein, human; D008565:Membrane Proteins