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Next generation sequencing of exceptional responders with BRAF-mutant melanoma: implications for sensitivity and resistance

Overview of attention for article published in BMC Cancer, February 2015
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Title
Next generation sequencing of exceptional responders with BRAF-mutant melanoma: implications for sensitivity and resistance
Published in
BMC Cancer, February 2015
DOI 10.1186/s12885-015-1029-z
Pubmed ID
Authors

Jennifer Wheler, Roman Yelensky, Gerald Falchook, Kevin B Kim, Patrick Hwu, Apostolia M Tsimberidou, Philip J Stephens, David Hong, Maureen T Cronin, Razelle Kurzrock

Abstract

Patients with BRAF mutation-positive advanced melanoma respond well to matched therapy with BRAF or MEK inhibitors, but often quickly develop resistance. Tumor tissue from ten patients with advanced BRAF mutation-positive melanoma who achieved partial response (PR) or complete response (CR) on BRAF and/or MEK inhibitors was analyzed using next generation sequencing (NGS) assay. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 734X with 99% of bases covered >100X. Three of the ten patients (median number of prior therapies = 2) attained prolonged CR (duration = 23.6+ to 28.7+ months); seven patients achieved either a PR or a short-lived CR. One patient who achieved CR ongoing at 28.7+ months and had tissue available close to the time of initiating BRAF inhibitor therapy had only a BRAF mutation. Abnormalities in addition to BRAF mutation found in other patients included: mutations in NRAS, APC and NF1; amplifications in BRAF, aurora kinase A, MYC, MITF and MET; deletions in CDKN2A/B and PAX5; and, alterations in RB1 and ATM. Heterogeneity between patients and molecular evolution within patients was noted. NGS identified potentially actionable DNA alterations that could account for resistance in patients with BRAF mutation-positive advanced melanoma who achieved a PR or CR but whose tumors later progressed. A subset of patients with advanced melanoma may harbor only a BRAF mutation and achieve a durable CR on BRAF pathway inhibitors.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 3%
United States 1 3%
Austria 1 3%
Unknown 35 92%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 32%
Student > Bachelor 3 8%
Other 3 8%
Student > Ph. D. Student 3 8%
Student > Master 3 8%
Other 4 11%
Unknown 10 26%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 24%
Biochemistry, Genetics and Molecular Biology 7 18%
Medicine and Dentistry 6 16%
Business, Management and Accounting 1 3%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Other 2 5%
Unknown 12 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 09 January 2016.
All research outputs
#17,753,591
of 22,800,560 outputs
Outputs from BMC Cancer
#4,958
of 8,296 outputs
Outputs of similar age
#173,345
of 255,027 outputs
Outputs of similar age from BMC Cancer
#87
of 149 outputs
Altmetric has tracked 22,800,560 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,296 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 34th percentile – i.e., 34% of its peers scored the same or lower than it.
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 255,027 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 149 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.