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Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA

Overview of attention for article published in Nature, April 2013
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • Good Attention Score compared to outputs of the same age and source (74th percentile)

Mentioned by

news
4 news outlets
blogs
4 blogs
policy
1 policy source
twitter
76 tweeters
patent
87 patents
facebook
3 Facebook pages

Citations

dimensions_citation
1302 Dimensions

Readers on

mendeley
1450 Mendeley
citeulike
13 CiteULike
Title
Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA
Published in
Nature, April 2013
DOI 10.1038/nature12065
Pubmed ID
Authors

Muhammed Murtaza, Sarah-Jane Dawson, Dana W. Y. Tsui, Davina Gale, Tim Forshew, Anna M. Piskorz, Christine Parkinson, Suet-Feung Chin, Zoya Kingsbury, Alvin S. C. Wong, Francesco Marass, Sean Humphray, James Hadfield, David Bentley, Tan Min Chin, James D. Brenton, Carlos Caldas, Nitzan Rosenfeld

Abstract

Cancers acquire resistance to systemic treatment as a result of clonal evolution and selection. Repeat biopsies to study genomic evolution as a result of therapy are difficult, invasive and may be confounded by intra-tumour heterogeneity. Recent studies have shown that genomic alterations in solid cancers can be characterized by massively parallel sequencing of circulating cell-free tumour DNA released from cancer cells into plasma, representing a non-invasive liquid biopsy. Here we report sequencing of cancer exomes in serial plasma samples to track genomic evolution of metastatic cancers in response to therapy. Six patients with advanced breast, ovarian and lung cancers were followed over 1-2 years. For each case, exome sequencing was performed on 2-5 plasma samples (19 in total) spanning multiple courses of treatment, at selected time points when the allele fraction of tumour mutations in plasma was high, allowing improved sensitivity. For two cases, synchronous biopsies were also analysed, confirming genome-wide representation of the tumour genome in plasma. Quantification of allele fractions in plasma identified increased representation of mutant alleles in association with emergence of therapy resistance. These included an activating mutation in PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) following treatment with paclitaxel; a truncating mutation in RB1 (retinoblastoma 1) following treatment with cisplatin; a truncating mutation in MED1 (mediator complex subunit 1) following treatment with tamoxifen and trastuzumab, and following subsequent treatment with lapatinib, a splicing mutation in GAS6 (growth arrest-specific 6) in the same patient; and a resistance-conferring mutation in EGFR (epidermal growth factor receptor; T790M) following treatment with gefitinib. These results establish proof of principle that exome-wide analysis of circulating tumour DNA could complement current invasive biopsy approaches to identify mutations associated with acquired drug resistance in advanced cancers. Serial analysis of cancer genomes in plasma constitutes a new paradigm for the study of clonal evolution in human cancers.

Twitter Demographics

The data shown below were collected from the profiles of 76 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 1,450 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 18 1%
United Kingdom 13 <1%
Japan 7 <1%
Germany 6 <1%
Netherlands 5 <1%
Spain 3 <1%
France 2 <1%
Ireland 2 <1%
Ukraine 2 <1%
Other 16 1%
Unknown 1376 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 385 27%
Student > Ph. D. Student 286 20%
Student > Master 134 9%
Student > Bachelor 132 9%
Other 97 7%
Other 252 17%
Unknown 164 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 417 29%
Medicine and Dentistry 354 24%
Biochemistry, Genetics and Molecular Biology 294 20%
Engineering 34 2%
Chemistry 22 2%
Other 116 8%
Unknown 213 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 114. 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 03 May 2022.
All research outputs
#268,111
of 21,152,972 outputs
Outputs from Nature
#15,769
of 87,324 outputs
Outputs of similar age
#1,861
of 174,172 outputs
Outputs of similar age from Nature
#237
of 917 outputs
Altmetric has tracked 21,152,972 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 87,324 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 96.9. This one has done well, scoring higher than 81% 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 174,172 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 917 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 74% of its contemporaries.