| Title |
Gastroesophageal junction adenocarcinoma displays abnormalities in homologous recombination and nucleotide excision repair
|
|---|---|
| Published in |
Lung Cancer: Targets and Therapy, February 2014
|
| DOI | 10.2147/lctt.s57594 |
| Pubmed ID | |
| Authors |
Robin I Dewalt, Kenneth A Kesler, Zane T Hammoud, LeeAnn Baldridge, Eyas M Hattab, Shadia I Jalal |
| Abstract |
Esophageal adenocarcinoma (EAC) continues to be a disease associated with high mortality. Among the factors leading to poor outcomes are innate resistance to currently available therapies, advanced stage at diagnosis, and complex biology. Platinum and ionizing radiation form the backbone of treatment for the majority of patients with EAC. Of the multiple processes involved in response to platinum chemotherapy or ionizing radiation, deoxyribonucleic acid (DNA) repair has been a major player in cancer sensitivity to these agents. DNA repair defects have been described in various malignancies. The purpose of this study was to determine whether alterations in DNA repair are present in EAC compared with normal gastroesophageal tissues. We analyzed the expression of genes involved in homologous recombination (HR), nonhomologous end-joining, and nucleotide excision repair (NER) pathways in 12 EAC tumor samples with their matched normal counterparts. These pathways were chosen because they are the main pathways involved in the repair of platinum- or ionizing-radiation-induced damage. In addition, abnormalities in these pathways have not been well characterized in EAC. We identified increased expression of at least one HR gene in eight of the EAC tumor samples. Alterations in the expression of EME1, a structure-specific endonuclease involved in HR, were the most prevalent, with messenger (m)RNA overexpression in six of the EAC samples. In addition, all EAC samples revealed decreased expression of at least one of numerous NER genes including XPC, XPA, DDB2, XPF, and XPG. Our study identified DNA repair dysregulation in EAC involving two critical pathways, HR and NER, and is the first demonstration of EME1 upregulation in any cancer. These DNA repair abnormalities have the potential to affect a number of processes such as genomic instability and therapy response, and the consequences of these defects deserve further study in EAC. |
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 % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 6 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 2 | 33% |
| Student > Ph. D. Student | 1 | 17% |
| Lecturer | 1 | 17% |
| Student > Doctoral Student | 1 | 17% |
| Unknown | 1 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 17% |
| Biochemistry, Genetics and Molecular Biology | 1 | 17% |
| Agricultural and Biological Sciences | 1 | 17% |
| Immunology and Microbiology | 1 | 17% |
| Chemistry | 1 | 17% |
| Other | 0 | 0% |
| Unknown | 1 | 17% |
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 17 February 2014.
All research outputs
#20,674,485
of 25,394,764 outputs
Outputs from Lung Cancer: Targets and Therapy
#98
of 128 outputs
Outputs of similar age
#244,760
of 322,857 outputs
Outputs of similar age from Lung Cancer: Targets and Therapy
#2
of 2 outputs
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