Breast Oncology Program, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109-5942, USA.
J Natl Cancer Inst. 2013 Sep 4;105(17):1332-4. doi: 10.1093/jnci/djt204. Epub 2013 Aug 19.
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.
福尔马林固定、石蜡包埋的肿瘤（FFPET）是用于基因型关联研究的有价值的 DNA 来源，并且通常是癌症临床试验中唯一的种系 DNA 资源。雌激素拮抗剂他莫昔芬被 CYP2D6 代谢为内消旋他莫昔芬，这导致了这样一种假设，即由于无法激活药物，某些 CYP2D6 基因型的患者可能无法从中受益。使用 FFPET 进行的这些研究提供了相互矛盾的结果。有人推测，由于体细胞肿瘤改变，使用 FFPET 确定的 CYP2D6 基因型可能不准确。在这项研究中，我们确定了来自 122 名乳腺癌患者的 3 种组织来源（FFPET；福尔马林固定、石蜡包埋的未受影响的淋巴结 [FFPELN]；和全血细胞 [WBC]）生成的 CYP2D6 基因型之间的一致性。与 WBC 相比，FFPET 和 FFPELN 基因型高度一致（>94%），预测的 CYP2D6 代谢表型也高度一致（>97%）。我们得出结论，从 FFPET 获得的 CYP2D6 基因型准确代表了患者的 CYP2D6 代谢表型。
