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Attention Score in Context
| Title |
Accuracy of four mononucleotide-repeat markers for the identification of DNA mismatch-repair deficiency in solid tumors
|
|---|---|
| Published in |
Journal of Translational Medicine, January 2018
|
| DOI | 10.1186/s12967-017-1376-4 |
| Pubmed ID | |
| Authors |
Yuko Takehara, Takeshi Nagasaka, Akihiro Nyuya, Tomoko Haruma, Junko Haraga, Yoshiko Mori, Keiichiro Nakamura, Toshiyoshi Fujiwara, C. Richard Boland, Ajay Goel |
| Abstract |
To screen tumors with microsatellite instability (MSI) arising due to DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are commonly used. In spite of its several strengths, the pentaplex assay is not robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome this challenge, we designed this study to develop and optimize a panel of four quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid tumors with dMMR, especially dMSH6. To improve the sensitivity for tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4 bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR [45 MutL homolog (MLH)1-deficient, 45 MutS protein homolog (MSH)2-deficient, and 15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In addition, we analyzed a cohort of 138 endometrial cancers (EC) by immunohistochemistry to determine MMR protein expression and validation of our new MSI assay. Using the criteria of ≥ 1 unstable markers as MSI-positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence interval (CI) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% CI = 91.5-97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a sensitivity of 92.7% (95% CI = 80.6-97.5%) and a specificity of 97.9% (95% CI = 92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC-validation set, Tetraplex detected dMSH6 tumors with a sensitivity of 86.7% (13 of 15 dMSH6 CRCs), which was subsequently validated in the EC test set as well (sensitivity, 75.0%; 6 of 8 dMSH6 ECs). Our newly optimized Tetraplex system will help offer a robust and highly sensitive assay for the identification of dMMR in solid tumors. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 28% |
| Other | 3 | 12% |
| Student > Ph. D. Student | 2 | 8% |
| Librarian | 1 | 4% |
| Student > Bachelor | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 9 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 7 | 28% |
| Medicine and Dentistry | 4 | 16% |
| Agricultural and Biological Sciences | 2 | 8% |
| Social Sciences | 1 | 4% |
| Unknown | 11 | 44% |
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 13 January 2018.
All research outputs
#15,488,947
of 23,016,919 outputs
Outputs from Journal of Translational Medicine
#2,258
of 4,027 outputs
Outputs of similar age
#270,779
of 443,072 outputs
Outputs of similar age from Journal of Translational Medicine
#48
of 69 outputs
Altmetric has tracked 23,016,919 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,027 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one is in the 31st percentile – i.e., 31% 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 443,072 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 69 others from the same source and published within six weeks on either side of this one. This one is in the 10th percentile – i.e., 10% of its contemporaries scored the same or lower than it.