| Title |
DNA damage response markers are differentially expressed in BRCA-mutated breast cancers
|
|---|---|
| Published in |
Breast Cancer Research and Treatment, February 2015
|
| DOI | 10.1007/s10549-015-3306-6 |
| Pubmed ID | |
| Authors |
Mohammed Aleskandarany, Daniela Caracappa, Christopher C. Nolan, R. Douglas Macmillan, Ian O. Ellis, Emad A. Rakha, Andrew R. Green |
| Abstract |
Cells have stringent DNA repair pathways that are specific for each different set of DNA lesions which is accomplished through the integration of complex array of proteins. However, BRCA-mutated breast cancer (BC) has defective DNA repair mechanisms. This study aims to investigate differential expression of a large panel of DNA repair markers to characterise DNA repair mechanisms in BRCA-associated tumours compared to sporadic tumours in an attempt to characterise these tumours in routine practice. Immunohistochemistry and tissue microarray technology were applied to a cohort of clinically annotated series of sporadic (n = 1849), BRCA1-mutated (n = 48), and BRCA2-mutated (n = 27) BC. The following DNA damage response (DDR) markers are used; BRCA1, BRCA2, RAD51, Ku70/Ku80, BARD, PARP1 (cleaved), PARP1 (non-cleaved), and P53 in addition to basal cytokeratins, ER, PR, and HER2. A significant proportion of BRCA1 tumours were positive for PARP1 (non-cleaved), and negative for BARD1 and RAD51 compared with sporadic BC. BRCA2 tumours were significantly positive for PARP1 (non-cleaved) compared with sporadic tumours. RAD51 was significantly higher in BRCA1 compared with BRCA2 tumours (p = 0.005). When BRCA1/2 BCs were compared to triple-negative (TN) sporadic tumours of the studied DDR proteins, BARD1 (p < 0.001), PARP1 (non-cleaved) (p < 0.001), and P53 (p = 0.002) remained significantly different in BRCA1/2 tumours compared with TN BC. DNA repair markers showed differential expression in BRCA-mutated tumours, with a substantial degree of disruption of DNA repair pathways in sporadic BC especially TN BC. DNA double-strand break (DSB) repair is assisted by PARP1 expression in BRCA-mutated tumours, whereas the loss of DSB repair via RAD51 is predominant in BRCA1 rather than BRCA2 BC. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | 33% |
| United States | 1 | 17% |
| Unknown | 3 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 83% |
| Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 67 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 1% |
| Belgium | 1 | 1% |
| Unknown | 65 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 16% |
| Student > Master | 10 | 15% |
| Student > Ph. D. Student | 9 | 13% |
| Student > Bachelor | 6 | 9% |
| Student > Doctoral Student | 5 | 7% |
| Other | 12 | 18% |
| Unknown | 14 | 21% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 33% |
| Biochemistry, Genetics and Molecular Biology | 12 | 18% |
| Agricultural and Biological Sciences | 11 | 16% |
| Chemical Engineering | 1 | 1% |
| Nursing and Health Professions | 1 | 1% |
| Other | 4 | 6% |
| Unknown | 16 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 01 March 2015.
All research outputs
#6,950,763
of 22,792,160 outputs
Outputs from Breast Cancer Research and Treatment
#1,517
of 4,655 outputs
Outputs of similar age
#78,920
of 255,121 outputs
Outputs of similar age from Breast Cancer Research and Treatment
#17
of 67 outputs
Altmetric has tracked 22,792,160 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 4,655 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.2. This one has gotten more attention than average, scoring higher than 66% 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 255,121 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 67 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.