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Concordance between CYP2D6 genotypes obtained from tumor-derived and germline DNA.

Abstract
Formalin-fixed, paraffin-embedded tumors (FFPETs) are a valuable source of DNA for genotype association studies and are often the only germline DNA resource from cancer clinical trials. The anti-estrogen tamoxifen is metabolized into endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6 genotypes may not receive benefit because of their inability to activate the drug. Studies testing this hypothesis using FFPETs have provided conflicting results. It has been postulated that CYP2D6 genotype determined using FFPET may not be accurate because of somatic tumor alterations. In this study, we determined the concordance between CYP2D6 genotypes generated using 3 tissue sources (FFPETs; formalin-fixed, paraffin-embedded unaffected lymph nodes [FFPELNs]; and whole blood cells [WBCs]) from 122 breast cancer patients. Compared with WBCs, FFPET and FFPELN genotypes were highly concordant (>94%), as were the predicted CYP2D6 metabolic phenotypes (>97%). We conclude that CYP2D6 genotypes obtained from FFPETs accurately represent the patient's CYP2D6 metabolic phenotype.
AuthorsJames M Rae, Meredith M Regan, Jacklyn N Thibert, Christina Gersch, Dafydd Thomas, Brian Leyland-Jones, Giuseppe Viale, Lajos Pusztai, Daniel F Hayes, Todd Skaar, Catherine Van Poznak
JournalJournal of the National Cancer Institute (J Natl Cancer Inst) Vol. 105 Issue 17 Pg. 1332-4 (Sep 04 2013) ISSN: 1460-2105 [Electronic] United States
PMID23958736 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents, Hormonal
  • DNA, Neoplasm
  • Estrogen Receptor Modulators
  • Tamoxifen
  • Cytochrome P-450 CYP2D6
Topics
  • Antineoplastic Agents, Hormonal (metabolism)
  • Blood Cells
  • Breast Neoplasms (enzymology, genetics)
  • Cytochrome P-450 CYP2D6 (genetics, metabolism)
  • DNA, Neoplasm (analysis)
  • Estrogen Receptor Modulators (metabolism)
  • Female
  • Genotype
  • Humans
  • Lymph Nodes
  • Tamoxifen (metabolism)

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