title: 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.
authors: Breast Oncology Program, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109-5942, USA. jimmyrae@umich.edu
authors: James M
authors: JM
authors: Rae
authors: Meredith M
authors: MM
authors: Regan
authors: Jacklyn N
authors: JN
authors: Thibert
authors: Christina
authors: C
authors: Gersch
authors: Dafydd
authors: D
authors: Thomas
authors: Brian
authors: B
authors: Leyland-Jones
authors: Giuseppe
authors: G
authors: Viale
authors: Lajos
authors: L
authors: Pusztai
authors: Daniel F
authors: DF
authors: Hayes
authors: Todd
authors: T
authors: Skaar
authors: Catherine
authors: C
authors: Van Poznak
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism; D001773:Blood Cells; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000032:analysis; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008198:Lymph Nodes; D013629:Tamoxifen / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6
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