Identification of targetable FGFR gene fusions in diverse cancers.

@article{Wu2013IdentificationOT,
  title={Identification of targetable FGFR gene fusions in diverse cancers.},
  author={Yi-Mi Wu and Fengyun Su and Shanker Kalyana-Sundaram and Nickolay A. Khazanov and Bushra Ateeq and Xuhong Cao and Robert J. Lonigro and Pankaj Vats and Rui Wang and Su-Fang Lin and Ann-Joy Cheng and Lakshmi Priya Kunju and Javed Siddiqui and Scott A. Tomlins and Peter Wyngaard and Seth Sadis and Sameek Roychowdhury and Maha H.A. Hussain and Felix Y. Feng and Mark M. Zalupski and Moshe Talpaz and Kenneth J. Pienta and Daniel R. Rhodes and Dan R. Robinson and Arul M. Chinnaiyan},
  journal={Cancer discovery},
  year={2013},
  volume={3 6},
  pages={
          636-47
        }
}
Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast cancer, and prostate cancer. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, we identified additional FGFR fusions with intact kinase domains in lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell… 

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  • Medicine, Biology
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
  • 2019
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References

SHOWING 1-10 OF 51 REFERENCES
Functionally Recurrent Rearrangements of the MAST Kinase and Notch Gene Families in Breast Cancer
TLDR
It is shown that recurrent gene rearrangements have key roles in subsets of carcinomas and suggest that transcriptome sequencing could identify individuals with rare, targetable gene fusions.
The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma.
TLDR
It is demonstrated that the FGFR3-TACC3 gene fusion is expressed in human cancer and generates an oncogenic protein that promotes tumorigenesis in glioblastoma.
Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma
TLDR
In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs, and a fusion gene detected in a small subset of human brain tumors encodes a potentially druggable target.
Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer.
Oncogenic FGFR3 gene fusions in bladder cancer
TLDR
As urothelial cell lines with FGFR3 fusions are extremely sensitive to FGFR-selective agents, the presence of a fusion gene may aid in selection of patients forFGFR-targeted therapy.
The transcriptional landscape and mutational profile of lung adenocarcinoma.
TLDR
The first large scale RNA sequencing study of lung adenocarcinoma is presented, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers.
Targeting mutant fibroblast growth factor receptors in cancer.
Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
TLDR
It is shown that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells.
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study
TLDR
The mutations present in advanced cancers can be identified by integrative high-throughput sequencing to enable biomarker-driven clinical trials and, ultimately, treatment and the authors tested this approach by extensively characterizing cancers in several patients and then convening a Sequencing Tumor Board of experts to determine the appropriate treatment.
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
TLDR
The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients, and the drug resulted in grade 1 or 2 gastrointestinal side effects.
...
...