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A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma

Overview of attention for article published in Genome Medicine, October 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (59th percentile)

Mentioned by

news
1 news outlet
twitter
10 tweeters

Citations

dimensions_citation
9 Dimensions

Readers on

mendeley
43 Mendeley
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Title
A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma
Published in
Genome Medicine, October 2016
DOI 10.1186/s13073-016-0366-0
Pubmed ID
Authors

Filemon S. Dela Cruz, Daniel Diolaiti, Andrew T. Turk, Allison R. Rainey, Alberto Ambesi-Impiombato, Stuart J. Andrews, Mahesh M. Mansukhani, Peter L. Nagy, Mariano J. Alvarez, Andrea Califano, Farhad Forouhar, Beata Modzelewski, Chelsey M. Mitchell, Darrell J. Yamashiro, Lianna J. Marks, Julia L. Glade Bender, Andrew L. Kung, Dela Cruz, Filemon S, Diolaiti, Daniel, Turk, Andrew T, Rainey, Allison R, Ambesi-Impiombato, Alberto, Andrews, Stuart J, Mansukhani, Mahesh M, Nagy, Peter L, Alvarez, Mariano J, Califano, Andrea, Forouhar, Farhad, Modzelewski, Beata, Mitchell, Chelsey M, Yamashiro, Darrell J, Marks, Lianna J, Bender, Julia L Glade, Kung, Andrew L

Abstract

Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient's tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis.

Twitter Demographics

The data shown below were collected from the profiles of 10 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 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Unknown 42 98%

Demographic breakdown

Readers by professional status Count As %
Unspecified 8 19%
Student > Ph. D. Student 8 19%
Researcher 7 16%
Student > Master 5 12%
Student > Doctoral Student 4 9%
Other 11 26%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 35%
Unspecified 10 23%
Agricultural and Biological Sciences 8 19%
Medicine and Dentistry 4 9%
Computer Science 3 7%
Other 3 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 23 March 2017.
All research outputs
#818,204
of 10,501,255 outputs
Outputs from Genome Medicine
#265
of 825 outputs
Outputs of similar age
#33,404
of 252,576 outputs
Outputs of similar age from Genome Medicine
#15
of 37 outputs
Altmetric has tracked 10,501,255 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 825 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.7. This one has gotten more attention than average, scoring higher than 67% 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 252,576 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.