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Oncogenic HER2 fusions in gastric cancer

Overview of attention for article published in Journal of Translational Medicine, April 2015
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About this Attention Score

  • Good Attention Score compared to outputs of the same age (72nd percentile)

Mentioned by

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2 tweeters
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1 patent

Citations

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15 Dimensions

Readers on

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35 Mendeley
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Title
Oncogenic HER2 fusions in gastric cancer
Published in
Journal of Translational Medicine, April 2015
DOI 10.1186/s12967-015-0476-2
Pubmed ID
Authors

De-Hua Yu, Lili Tang, Hua Dong, Zhengwei Dong, Lianhai Zhang, Jiangang Fu, Xinying Su, Tianwei Zhang, Haihua Fu, Lu Han, Liang Xie, Hao Chen, Ziliang Qian, Guanshan Zhu, Jia Wang, Qingqing Ye, Jingchuan Zhang, Xiaolu Yin, Xiaolin Zhang, Jiafu Ji, Qunsheng Ji

Abstract

Genetic amplification of HER2 drives tumorigenesis and cancer progression in a subset of patients with gastric cancer (GC), and treatment with trastuzumab, a humanized HER2-neutralizing antibody, improves the overall survival rate of HER2-positive patients. However, a considerable portion of the patients does not respond to trastuzumab and the molecular mechanisms underlying the intrinsic resistance to anti-HER2 therapy in GC is not fully understood. We performed whole-transcriptome sequencing on 21 HER2-positive tumor specimens from Chinese GC patients. Whole genome sequencing was performed on the three samples with HER2 fusion to discover the DNA integration structure. A multicolor FISH assay for HER2 split screening was conducted to confirm HER2 fusion and IHC (HercepTest™) was used to detect the membranous expression of HER2. Fusion cDNA were transfected into NIH/3T3 cells and generate stable cell line by lentivirus. The expression of exogenous HER2 fusion proteins and pHER2 were examined by western blot analysis. In vitro efficacy studies were also conducted by PD assay and softagar assay in cell line expression wild type and fusion HER2. T-DM1 was used to assess its binding to NIH/3T3 cells ectopically expressing wild-type and fusion HER2. Finally, the anti-tumor efficacy of trastuzumab was tested in NIH/3 T3 xenografts expressing the HER2 fusion variants. We identified three new HER2 fusions with ZNF207, MDK, or NOS2 in 21 HER2-amplified GC samples (14%; 3/21). Two of the fusions, ZNF207-HER2, and MDK-HER2, which are oncogenic, lead to aberrant activation of HER2 kinase. Treatment with trastuzumab inhibited tumor growth significantly in xenografts expressing MDK-HER2 fusion. In contrast, trastuzumab had no effect on the growth of xenografts expressing ZNF207-HER2 fusion, due to its inability to bind to trastuzumab. Our results provide the molecular basis of a novel resistance mechanism to trastuzumab-based anti-HER2 therapy, supporting additional molecule stratification within HER2-positive GC patients for more effective therapy options.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 23%
Student > Master 8 23%
Student > Bachelor 3 9%
Student > Ph. D. Student 2 6%
Student > Doctoral Student 1 3%
Other 1 3%
Unknown 12 34%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 17%
Medicine and Dentistry 5 14%
Agricultural and Biological Sciences 4 11%
Psychology 3 9%
Business, Management and Accounting 2 6%
Other 3 9%
Unknown 12 34%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2022.
All research outputs
#5,942,800
of 22,130,231 outputs
Outputs from Journal of Translational Medicine
#873
of 3,838 outputs
Outputs of similar age
#67,983
of 249,904 outputs
Outputs of similar age from Journal of Translational Medicine
#1
of 1 outputs
Altmetric has tracked 22,130,231 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 3,838 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.3. This one has done well, scoring higher than 76% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 249,904 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them