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Whole-genome approach implicates CD44in cellular resistance to carboplatin

Overview of attention for article published in Human Genomics, January 2009
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Title
Whole-genome approach implicates CD44in cellular resistance to carboplatin
Published in
Human Genomics, January 2009
DOI 10.1186/1479-7364-3-2-128
Pubmed ID
Authors

Sunita J. Shukla, Shiwei Duan, Xiaolin Wu, Judith A. Badner, Kristen Kasza, M. Eileen Dolan

Abstract

Carboplatin is a chemotherapeutic agent used in the management of many cancers, yet treatment is limited by resistance and toxicities. To achieve a better understanding of the genetic contribution to carboplatin resistance or toxicities, lymphoblastoid cell lines from 34 large Centre d'Etude du Polymorphisme Humain pedigrees were utilised to evaluate interindividual variation in carboplatin cytotoxicity. Significant heritability, ranging from 0.17-0.36 (p = 1 x 10(-7) to 9 x 10(-4)), was found for cell growth inhibition following 72-hour treatment at each carboplatin concentration (10, 20, 40 and 80 microM) and IC(50) (concentration for 50 per cent cell growth inhibition). Linkage analysis revealed 11 regions with logarithm of odds (LOD) scores greater than 1.5. The highest LOD score on chromosome 11 (LOD = 3.36, p = 4.2 x 10(-5)) encompasses 65 genes within the 1 LOD confidence interval for the carboplatin IC 50 . We further analysed the IC(50) phenotype with a linkage-directed association analysis using 71 unrelated HapMap and Perlegen cell lines and identified 18 single nucleotide polymorphisms within eight genes that were significantly associated with the carboplatin IC(50) (p < 3.6 x 10(-5); false discovery rate <5 per cent). Next, we performed linear regression on the baseline expression and carboplatin IC(50) values of the eight associated genes, which identified the most significant correlation between CD44 expression and IC(50) (r(2)= 0.20; p = 6 x 10(-4)). The quantitative real-time polymerase chain reaction further confirmed a statistically significant difference in CD44 expression levels between carboplatin-resistant and -sensitive cell lines (p = 5.9 x 10(-3)). Knockdown of CD44 expression through small interfering RNA resulted in increased cellular sensitivity to carboplatin (p < 0.01). Our whole-genome approach using molecular experiments identified CD44 as being important in conferring cellular resistance to carboplatin.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 19 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 5%
Unknown 18 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 32%
Student > Doctoral Student 3 16%
Student > Ph. D. Student 3 16%
Student > Bachelor 2 11%
Other 1 5%
Other 1 5%
Unknown 3 16%
Readers by discipline Count As %
Agricultural and Biological Sciences 10 53%
Pharmacology, Toxicology and Pharmaceutical Science 2 11%
Biochemistry, Genetics and Molecular Biology 1 5%
Medicine and Dentistry 1 5%
Materials Science 1 5%
Other 0 0%
Unknown 4 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 14 July 2011.
All research outputs
#8,535,472
of 25,374,917 outputs
Outputs from Human Genomics
#211
of 564 outputs
Outputs of similar age
#52,785
of 183,281 outputs
Outputs of similar age from Human Genomics
#3
of 5 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 564 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has gotten more attention than average, scoring higher than 53% 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 183,281 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.