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

James 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

Research output: Contribution to journalArticlepeer-review


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, paraffinembedded 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.

Original languageEnglish
Pages (from-to)1332-1334
Number of pages3
JournalJournal of the National Cancer Institute
Issue number17
Publication statusPublished - Sep 4 2013

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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