Publications by authors named "Teri M Plona"

3 Publications

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Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA) Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

Int J Mol Sci 2020 Jan 30;21(3). Epub 2020 Jan 30.

Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

To ensure accuracy of (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR "slippage". Direct sequencing was accurate, but this method led to ambiguous electrophoregrams, hampering interpretation of heterozygotes. Gel sizing, pyrosequencing, and array-based technologies were less concordant. Pharmacoscan genotyping was concordant, but it does not ascertain genotypes that are common in African populations. Method-based genotyping differences were also observed in the publication record ( < 0.0046), although fragment analysis and direct sequencing were concordant ( = 0.11). Genotyping errors can have significant consequences in a clinical setting. At the present time, we recommend that all genotyping for this allele be conducted with fluorescent PCR (fPCR).
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http://dx.doi.org/10.3390/ijms21030896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037496PMC
January 2020

Pharmacogenomics Implementation at the National Institutes of Health Clinical Center.

J Clin Pharmacol 2017 Oct;57 Suppl 10:S67-S77

Pharmacy Department, NIH Clinical Center, Bethesda, MD, USA.

The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol. In the second phase, we implemented genotyping for drug-metabolizing enzymes and transporters: SLCO1B1 for CDS of simvastatin and TPMT for CDS of mercaptopurine, azathioprine, and thioguanine. The purpose of this review is to describe the implementation process, which involves clinical, laboratory, informatics, and policy decisions pertinent to the NIH CC.
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http://dx.doi.org/10.1002/jcph.993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5657584PMC
October 2017

Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair.

J Med Genet 2011 Mar 19;48(3):168-76. Epub 2010 Nov 19.

Genetic Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland 20892-4258, USA.

Background: The frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a four decade natural history study.

Methods: All 106 XP patients admitted to the National Institutes of Health from 1971 to 2009 were evaluated from clinical records and follow-up.

Results: In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10,000-fold and melanoma was increased 2000-fold in patients under age 20. The 9 year median age at diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly younger than the 22 year median age at diagnosis of first melanoma (n=38)-a relative age reversal from the general population suggesting different mechanisms of carcinogenesis between NMSC and melanoma. XP patients with pronounced burning on minimal sun exposure (n=65) were less likely to develop skin cancer than those who did not. This may be related to the extreme sun protection they receive from an earlier age, decreasing their total ultraviolet exposure. Progressive neurologic degeneration was present in 24% (n=25) with 16/25 in complementation group XP-D. The most common causes of death were skin cancer (34%, n=10), neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). The median age at death (29 years) in XP patients with neurodegeneration was significantly younger than those XP patients without neurodegeneration (37 years) (p=0.02).

Conclusion: This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the aetiology of skin cancer and neurologic degeneration.
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http://dx.doi.org/10.1136/jmg.2010.083022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235003PMC
March 2011