The tyrosine kinase adaptor protein FRS2 is oncogenic and amplified in high-grade serous ovarian cancer

Leo Y. Luo; Eejung Kim; Hiu Wing Cheung; Barbara A. Weir; Gavin P. Dunn; Rhine R. Shen; William C. Hahn

doi:10.1158/1541-7786.MCR-14-0407

The tyrosine kinase adaptor protein FRS2 is oncogenic and amplified in high-grade serous ovarian cancer

Leo Y. Luo, Eejung Kim, Hiu Wing Cheung, Barbara A. Weir, Gavin P. Dunn, Rhine R. Shen, William C. Hahn

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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.

Original language	English
Pages (from-to)	502-509
Number of pages	8
Journal	Molecular Cancer Research
Volume	13
Issue number	3
DOIs	https://doi.org/10.1158/1541-7786.MCR-14-0407
State	Published - Mar 1 2015

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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.",

author = "Luo, {Leo Y.} and Eejung Kim and Cheung, {Hiu Wing} and Weir, {Barbara A.} and Dunn, {Gavin P.} and Shen, {Rhine R.} and Hahn, {William C.}",

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AU - Luo, Leo Y.

AU - Kim, Eejung

AU - Cheung, Hiu Wing

AU - Weir, Barbara A.

AU - Dunn, Gavin P.

AU - Shen, Rhine R.

AU - Hahn, William C.

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AB - 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.

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The tyrosine kinase adaptor protein FRS2 is oncogenic and amplified in high-grade serous ovarian cancer

Abstract

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