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Identification by array comparative genomic hybridization of a new amplicon on chromosome 17q highly recurrent in BRCA1 mutated triple negative breast cancer

Overview of attention for article published in Breast Cancer Research, November 2014
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60 Mendeley
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Title
Identification by array comparative genomic hybridization of a new amplicon on chromosome 17q highly recurrent in BRCA1 mutated triple negative breast cancer
Published in
Breast Cancer Research, November 2014
DOI 10.1186/s13058-014-0466-y
Pubmed ID
Authors

Sébastien Toffoli, Isabelle Bar, Fadi Abdel-Sater, Paul Delrée, Pascale Hilbert, Frédéric Cavallin, Fabrice Moreau, Wim Van Criekinge, Magali Lacroix-Triki, Mario Campone, Anne-Laure Martin, Henri Roché, Jean-Pascal Machiels, Javier Carrasco, Jean-Luc Canon

Abstract

IntroductionTriple Negative Breast Cancers (TNBC) represent about 12% to 20% of all breast cancers (BC) and have a worse outcome compared to other BC subtypes. TNBC often show a deficiency in DNA double-strand break repair mechanisms. This is generally related to the inactivation of a repair enzymatic complex involving BRCA1 caused either by genetic mutations, epigenetic modifications or by post-transcriptional regulations.The identification of new molecular biomarkers that would allow the rapid identification of BC presenting a BRCA1 deficiency could be useful to select patients who could benefit from PARP inhibitors, alkylating agents or platinum-based chemotherapy.MethodsGenomic DNA from 131 formalin-fixed paraffin-embedded (FFPE) tumors (luminal A and B, HER2+ and triple negative BC) with known BRCA1 mutation status or unscreened for BRCA1 mutation were analysed by array Comparative Genomic Hybridization (array CGH). One highly significant and recurrent gain in the 17q25.3 genomic region was analysed by fluorescent in situ hybridization (FISH). Expression of the genes of the 17q25.3 amplicon was studied using customized Taqman low density arrays and single Taqman assays (Applied Biosystems).ResultsWe identified by array CGH and confirmed by FISH a gain in the 17q25.3 genomic region in 90% of the BRCA1 mutated tumors. This chromosomal gain was present in only 28.6% of the BRCA1 non-mutated TNBC, 26.7% of the unscreened TNBC, 13.6% of the luminal B, 19.0% of the HER2+ and 0% of the luminal A breast cancers. The 17q25.3 gain was also detected in 50% of the TNBC with BRCA1 promoter methylation. Interestingly, BRCA1 promoter methylation was never detected in BRCA1 mutated BC. Gene expression analyses of the 17q25.3 sub-region showed a significant over-expression of 17 genes in BRCA1 mutated TNBC (n¿=¿15) as compared to the BRCA1 non mutated TNBC (n¿=¿13).ConclusionsIn this study, we have identified by array CGH and confirmed by FISH a recurrent gain in 17q25.3 significantly associated to BRCA1 mutated TNBC. Up-regulated genes in the 17q25.3 amplicon might represent potential therapeutic targets and warrant further investigation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Germany 1 2%
Belgium 1 2%
Unknown 57 95%

Demographic breakdown

Readers by professional status Count As %
Student > Master 12 20%
Student > Ph. D. Student 10 17%
Researcher 9 15%
Student > Bachelor 8 13%
Other 3 5%
Other 11 18%
Unknown 7 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 40%
Medicine and Dentistry 13 22%
Agricultural and Biological Sciences 7 12%
Computer Science 3 5%
Chemistry 2 3%
Other 3 5%
Unknown 8 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 26 November 2014.
All research outputs
#15,739,529
of 25,373,627 outputs
Outputs from Breast Cancer Research
#1,386
of 2,052 outputs
Outputs of similar age
#200,360
of 368,570 outputs
Outputs of similar age from Breast Cancer Research
#24
of 49 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,052 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 30th percentile – i.e., 30% 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 368,570 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.