Scientific Publications

In vivo multiplexed interrogation of amplified genes identifies GAB2 as an ovarian cancer oncogene.

Publication TypeJournal Article
AuthorsDunn, GP, Cheung HW, Agarwalla PK, Thomas S., Zektser Y., Karst AM, Boehm JS, Weir BA, Berlin AM, Zou L., Getz G., Liu JF, Hirsch M., Vazquez F., Root DE, Beroukhim R., Drapkin R., and Hahn WC
AbstractHigh-grade serous ovarian cancers are characterized by widespread recurrent copy number alterations. Although some regions of copy number change harbor known oncogenes and tumor suppressor genes, the genes targeted by the majority of amplified or deleted regions in ovarian cancer remain undefined. Here we systematically tested amplified genes for their ability to promote tumor formation using an in vivo multiplexed transformation assay. We identified the GRB2-associated binding protein 2 (GAB2) as a recurrently amplified gene that potently transforms immortalized ovarian and fallopian tube secretory epithelial cells. Cancer cell lines overexpressing GAB2 require GAB2 for survival and show evidence of phosphatidylinositol 3-kinase (PI3K) pathway activation, which was required for GAB2-induced transformation. Cell lines overexpressing GAB2 were as sensitive to PI3K inhibition as cell lines harboring mutant PIK3CA. Together, these observations nominate GAB2 as an ovarian cancer oncogene, identify an alternative mechanism to activate PI3K signaling, and underscore the importance of PI3K signaling in this cancer.
Year of Publication2014
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue3
Pages1102-7
Date Published (YYYY/MM/DD)2014/01/21
ISSN Number0027-8424
DOI10.1073/pnas.1311909111
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/24385586?dopt=Abstract