Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA

被引：29

作者：

Rae, James M. ^{[1
,2
,3
]}

Regan, Meredith M. ^{[5
,6
]}

Thibert, Jacklyn N. ^{[1
]}

Gersch, Christina ^{[1
]}

Thomas, Dafydd ^{[1
,4
]}

Leyland-Jones, Brian ^{[7
]}

Viale, Giuseppe ^{[8
]}

Pusztai, Lajos ^{[9
]}

Hayes, Daniel F. ^{[1
,2
]}

Skaar, Todd ^{[8
,10
]}

Van Poznak, Catherine ^{[1
,2
]}

机构：

[1] Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

[5] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[6] Harvard Univ, Sch Med, Boston, MA USA

[7] Sanford Hlth & Res, Sioux Falls, SD USA

[8] Univ Milan, Milan, Italy

[9] Yale Univ, Sch Med, New Haven, CT USA

[10] Indiana Univ, Div Clin Pharmacol, Indianapolis, IN 46204 USA

来源：

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE | 2013年 / 105卷 / 17期

关键词：

RESPONSIVE BREAST-CANCER; POSTMENOPAUSAL WOMEN; TAMOXIFEN RESPONSE; RE CYP2D6; UGT2B7; GENOTYPE; RECURRENCE; METABOLISM; OUTCOMES; RISK;

D O I：

10.1093/jnci/djt204

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1332 / 1334

页数：3

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