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HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures

Overview of attention for article published in Nature Medicine, March 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (94th percentile)

Citations

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770 Dimensions

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888 Mendeley
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6 CiteULike
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Title
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Published in
Nature Medicine, March 2017
DOI 10.1038/nm.4292
Pubmed ID
Authors

Helen Davies, Dominik Glodzik, Sandro Morganella, Lucy R Yates, Johan Staaf, Xueqing Zou, Manasa Ramakrishna, Sancha Martin, Sandrine Boyault, Anieta M Sieuwerts, Peter T Simpson, Tari A King, Keiran Raine, Jorunn E Eyfjord, Gu Kong, Åke Borg, Ewan Birney, Hendrik G Stunnenberg, Marc J van de Vijver, Anne-Lise Børresen-Dale, John W M Martens, Paul N Span, Sunil R Lakhani, Anne Vincent-Salomon, Christos Sotiriou, Andrew Tutt, Alastair M Thompson, Steven Van Laere, Andrea L Richardson, Alain Viari, Peter J Campbell, Michael R Stratton, Serena Nik-Zainal

Abstract

Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.

X Demographics

X Demographics

The data shown below were collected from the profiles of 248 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 888 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 3 <1%
Germany 1 <1%
Italy 1 <1%
Ghana 1 <1%
Sweden 1 <1%
Netherlands 1 <1%
Canada 1 <1%
Finland 1 <1%
Spain 1 <1%
Other 1 <1%
Unknown 876 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 212 24%
Student > Ph. D. Student 143 16%
Student > Master 75 8%
Student > Bachelor 71 8%
Other 51 6%
Other 125 14%
Unknown 211 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 302 34%
Agricultural and Biological Sciences 142 16%
Medicine and Dentistry 136 15%
Computer Science 21 2%
Engineering 10 1%
Other 56 6%
Unknown 221 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 508. 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 28 December 2023.
All research outputs
#50,856
of 25,584,565 outputs
Outputs from Nature Medicine
#324
of 9,382 outputs
Outputs of similar age
#1,119
of 323,004 outputs
Outputs of similar age from Nature Medicine
#5
of 68 outputs
Altmetric has tracked 25,584,565 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 9,382 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 105.6. This one has done particularly well, scoring higher than 96% 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 323,004 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 99% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 94% of its contemporaries.