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1.
Cell Rep ; 31(5): 107550, 2020 05 05.
Article in English | MEDLINE | ID: mdl-32375028

ABSTRACT

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB but low clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure.


Subject(s)
Biomarkers, Tumor/genetics , High-Throughput Nucleotide Sequencing , Lung Neoplasms/genetics , Tumor Burden/genetics , Urinary Bladder Neoplasms/genetics , Biopsy/methods , High-Throughput Nucleotide Sequencing/methods , Humans , Lung Neoplasms/pathology , Mutation/genetics , Urinary Bladder Neoplasms/pathology
2.
Environ Toxicol Chem ; 35(8): 1995-2002, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27442160

ABSTRACT

The bald eagle (Haliaeetus leucocephalus) is an extensively researched tertiary predator. Studies have delineated information about its life history and the influences of various stressors on its reproduction. Due to the bald eagle's position at the top of the food web, it is susceptible to biomagnification of xenobiotics. The Michigan Department of Environmental Quality implemented a program in 1999 to monitor persistent chemicals including polychlorinated biphenols (PCBs) and dichlorodiphenyltrichloroethane (DDE). The objectives of the present study were to evaluate spatial and temporal trends of PCBs and organochlorine pesticides in nestling bald eagles of Michigan. The authors' study found that concentrations of PCBs and DDE were higher in Great Lakes areas with Lakes Michigan and Lake Huron having the highest concentrations of DDE and Lake Erie having the highest concentrations of PCBs. Temporally (1987-1992, 1999-2003, and 2004-2008) the present study found declines in PCB and DDE concentrations with a few exceptions. Continued monitoring of Michigan bald eagle populations is suggested for a couple of reasons. First, nestling blood contaminant levels are an appropriate method to monitor ecosystem contaminant levels. Second, from 1999 to 2008 PCB and DDE concentrations for 30% and 40%, respectively, of the nestling eagles sampled were above the no observable adverse effect level (NOAEL) for bald eagles. Lastly, with the continued development and deployment of new chemistries a continuous long term monitoring program is an invaluable resource. Environ Toxicol Chem 2016;35:1995-2002. © 2016 SETAC.

3.
Environ Toxicol Chem ; 35(8): 2134, 2016 08.
Article in English | MEDLINE | ID: mdl-25677528

ABSTRACT

Retraction: 'Using bald eagles to track spatial (1999-2008) and temporal (1987-1992, 1999-2003, and 2004-2008) trends of contaminants in Michigan's aquatic ecosystems' by Michael R. Wierda, Katherine F. Leith, Teryl G. Grubb, James G. Sikarskie, David A. Best, and William Bowerman The above article from Environmental Toxicology and Chemistry, published online on 10 February 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, G.A. Burton, Jr., SETAC and Wiley Periodicals, Inc. The retraction has been agreed since the authors determined that some of the plasma samples run at Clemson University had failed quality assurance/quality control and were retested. The concentrations have since been corrected and validated. Reference Wierda MR, Leith KF, Grubb TG, Sikarskie JG, Best DA, Bowerman W. 2015. Using bald eagles to track spatial (1999-2008) and temporal (1987-1992, 1999-2003, and 2004-2008) trends of contaminants in Michigan's aquatic ecosystems. Environ ToxicolChem doi:10.1002/etc.2859.

4.
Chemosphere ; 80(1): 7-12, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20416924

ABSTRACT

Monitoring of contaminants in the environment is an important part of understanding the fate of ecosystems after a chemical insult. Frequently, such monitoring efforts result in datasets with observations below the detection limit (DL) that are reported as 'non-detect' or '

Subject(s)
Dichlorodiphenyl Dichloroethylene/blood , Environmental Pollutants/blood , Models, Statistical , Polychlorinated Biphenyls/blood , Animals , Eagles , Environmental Monitoring , Environmental Pollutants/chemistry , Limit of Detection , Michigan
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