ArticleProceedings of the National Academy of Sciences of the United States of America2015
Recurrent BCAM-AKT2 fusion gene leads to a constitutively activated AKT2 fusion kinase in high-grade serous ovarian carcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Oligoclonal B cell expansion and passenger fusion genes predict response to Nivolumab in recurrent ovarian cancer: phase II Kyoto trial.Cancer immunology, immunotherapy : CII · 2026Trial
- BCAM-AKT2 fusion protein promotes unfolded protein response driven oncogenic signaling in SKOV3 epithelial ovarian cancer cell line.PloS one · 2026Article
- The Aptamer bi-(AID-1-T) Synergizes with Radiation to Inhibit Proliferation of Human Glioma Cells.Pharmaceutics · 2025Article
- BCAM (basal cell adhesion molecule) protein expression in different tumor populations.Discover oncology · 2024Article
- The Role of Lutheran/Basal Cell Adhesion Molecule in Hematological Diseases and Tumors.International journal of molecular sciences · 2024Review
- Machine Learning-Enhanced Extraction of Biomarkers for High-Grade Serous Ovarian Cancer from Proteomics Data.Scientific data · 2024Article
- Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.Advanced healthcare materials · 2023Article
- Discovery of antibodies and cognate surface targets for ovarian cancer by surface profiling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pattern recognition in the landscape of seemingly random chimeric transcripts.Computational and structural biotechnology journal · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- Identification of a Novel Oncogenic Fusion GeneInternational journal of molecular sciences · 2022Article
- Fusion Gene Detection Using Whole-Exome Sequencing Data in Cancer Patients.Frontiers in genetics · 2022Article
- Fusion genes in gynecologic tumors: the occurrence, molecular mechanism and prospect for therapy.Cell death & disease · 2021Review
- Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a NovelCancer discovery · 2019Article
- Identification of recurrent fusion genes across multiple cancer types.Scientific reports · 2019Article
- Transcriptomic and genomic profiling of early-stage ovarian carcinomas associated with histotype and overall survival.Oncotarget · 2018Article
- Identification of novel cyclin gene fusion transcripts in endometrioid ovarian carcinomas.International journal of cancer · 2018Article
- Internalization of CD239 highly expressed in breast cancer cells: a potential antigen for antibody-drug conjugates.Scientific reports · 2018Article
- Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway.Molecular cancer · 2018Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
High-grade serous ovarian cancer (HGSC) is among the most lethal forms of cancer in women. Excessive genomic rearrangements, which are expected to create fusion oncogenes, are the hallmark of this cancer. Here we report a cancer-specific gene fusion between BCAM, a membrane adhesion molecule, and AKT2, a key kinase in the PI3K signaling pathway. This fusion is present in 7% of the 60 patient cancers tested, a significant frequency considering the highly heterogeneous nature of this malignancy. Further, we provide direct evidence that BCAM-AKT2 is translated into an in-frame fusion protein in the patient's tumor. The resulting AKT2 fusion kinase is membrane-associated, constitutively phosphorylated, and activated as a functional kinase in cells. Unlike endogenous AKT2, whose activity is tightly regulated by external stimuli, BCAM-AKT2 escapes the regulation from external stimuli. Moreover, a BCAM-AKT2 fusion gene generated via chromosomal translocation using the CRISPR/Cas9 system leads to focus formation in both OVCAR8 and HEK-293T cell lines, suggesting that BCAM-AKT2 is oncogenic. Together, the results indicate that BCAM-AKT2 expression is a new mechanism of AKT2 kinase activation in HGSC. BCAM-AKT2 is the only fusion gene in HGSC that is proven to translate an aberrant yet functional kinase fusion protein with oncogenic properties. This recurrent genomic alteration is a potential therapeutic target and marker of a clinically relevant subtype for tailored therapy of HGSC.
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