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Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing

Overview of attention for article published in Breast Cancer Research and Treatment, March 2017
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Title
Detection of ESR1 mutations in plasma and tumors from metastatic breast cancer patients using next-generation sequencing
Published in
Breast Cancer Research and Treatment, March 2017
DOI 10.1007/s10549-017-4190-z
Pubmed ID
Authors

Takehiro Yanagawa, Naofumi Kagara, Tomohiro Miyake, Tomonori Tanei, Yasuto Naoi, Masafumi Shimoda, Kenzo Shimazu, Seung Jin Kim, Shinzaburo Noguchi

Abstract

Liquid biopsy using digital PCR (dPCR) has been widely used for the screening of ESR1 mutations, since they are frequently identified in the hotspot. However, dPCR is limited to the known mutations. Therefore, we aimed to analyze the utility of next-generation sequencing (NGS) to discover novel ESR1 mutations. Whole exon sequencing of the ESR1 gene using NGS was performed in 16 primary and 47 recurrent tumor samples and 38 plasma samples from hormone receptor-positive metastatic breast cancer patients. Functional analyses were then performed for the novel mutations we detected. We identified no mutations in primary tumors and six mutations in five recurrent tumors, including three types of known mutations (Y537C, Y537N, and D538G) and two novel mutations (E279V and G557R). We also identified seven mutations in five plasma samples, including three types of known mutations (S463P, Y537S, and D538G) and one mutation not reported in COSMIC database (L536H). All nine patients with ESR1 mutations were treated with aromatase inhibitors (AIs) prior to sampling, and the mutations were frequently detected in patients who received AI treatments in the metastatic setting. Among the three novel mutations (E279V, L536H, and G557R), L536H, but not E279V and G557R, showed ligand-independent activity. All three mutant proteins showed nuclear localization and had no relation with non-genomic ER pathways. Although the molecular mechanisms of the E279V and G557R mutations remain unclear, our data suggest the utility of NGS as a liquid biopsy for metastatic breast cancer patients and the potential to identify novel ESR1 mutations.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Netherlands 1 2%
Unknown 47 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 21%
Researcher 10 21%
Student > Master 5 10%
Other 5 10%
Student > Doctoral Student 4 8%
Other 7 15%
Unknown 7 15%
Readers by discipline Count As %
Medicine and Dentistry 17 35%
Biochemistry, Genetics and Molecular Biology 13 27%
Agricultural and Biological Sciences 2 4%
Computer Science 1 2%
Physics and Astronomy 1 2%
Other 3 6%
Unknown 11 23%

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 20 February 2018.
All research outputs
#10,032,567
of 12,538,691 outputs
Outputs from Breast Cancer Research and Treatment
#2,468
of 3,141 outputs
Outputs of similar age
#202,314
of 271,237 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#45
of 59 outputs
Altmetric has tracked 12,538,691 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,141 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one is in the 12th percentile – i.e., 12% 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 271,237 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 59 others from the same source and published within six weeks on either side of this one. This one is in the 13th percentile – i.e., 13% of its contemporaries scored the same or lower than it.