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Mol Cancer Res. 2015 Mar;13(3):502-9. doi: 10.1158/1541-7786.MCR-14-0407. Epub 2014 Nov 3.

The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer.

Author information

  • 1Health 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.
  • 2Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
  • 3Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
  • 4Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts.
  • 5Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri.
  • 6Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Astellas Pharma U.S. Inc., Santa Monica, California.
  • 7Broad 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.

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.

IMPLICATIONS:

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.

PMID:
25368431
PMCID:
PMC4369154
DOI:
10.1158/1541-7786.MCR-14-0407
[PubMed - indexed for MEDLINE]
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