Data from Characterization of <i>ERG</i>, <i>AR</i> and <i>PTEN</i> Gene Status in Circulating Tumor Cells from Patients with Castration-Resistant Prostate Cancer

Abstract

&lt;div&gt;Abstract&lt;p&gt;Hormone-driven expression of the &lt;i&gt;ERG&lt;/i&gt; oncogene after fusion with &lt;i&gt;TMPRSS2&lt;/i&gt; occurs in 30% to 70% of therapy-naive prostate cancers. Its relevance in castration-resistant prostate cancer (CRPC) remains controversial as &lt;i&gt;ERG&lt;/i&gt; is not expressed in some &lt;i&gt;TMPRSS2-ERG&lt;/i&gt; androgen-independent xenograft models. However, unlike these models, CRPC patients have an increasing prostate-specific antigen, indicating active androgen receptor signaling. Here, we collected blood every month from 89 patients (54 chemotherapy-naive patients and 35 docetaxel-treated patients) treated in phase I/phase II clinical trials of an orally available, highly specific CYP17 inhibitor, abiraterone acetate, that ablates the synthesis of androgens and estrogens that drive &lt;i&gt;TMPRSS2-ERG&lt;/i&gt; fusions. We isolated circulating tumor cells (CTC) by anti–epithelial cell adhesion molecule immunomagnetic selection followed by cytokeratin and CD45 immunofluorescence and 4′,6-diamidino-2-phenylindole staining. We used multicolor fluorescence &lt;i&gt;in situ&lt;/i&gt; hybridization to show that CRPC CTCs, metastases, and prostate tissue invariably had the same &lt;i&gt;ERG&lt;/i&gt; gene status as therapy-naive tumors (&lt;i&gt;n&lt;/i&gt; = 31). We then used quantitative reverse transcription–PCR to show that &lt;i&gt;ERG&lt;/i&gt; expression was maintained in CRPC. We also observed homogeneity in &lt;i&gt;ERG&lt;/i&gt; gene rearrangement status in CTCs (&lt;i&gt;n&lt;/i&gt; = 48) in contrast to significant heterogeneity of &lt;i&gt;AR&lt;/i&gt; copy number gain and &lt;i&gt;PTEN&lt;/i&gt; loss, suggesting that rearrangement of &lt;i&gt;ERG&lt;/i&gt; may be an earlier event in prostate carcinogenesis. We finally report a significant association between &lt;i&gt;ERG&lt;/i&gt; rearrangements in therapy-naive tumors, CRPCs, and CTCs and magnitude of prostate-specific antigen decline (&lt;i&gt;P&lt;/i&gt; = 0.007) in CRPC patients treated with abiraterone acetate. These data confirm that CTCs are malignant in origin and indicate that hormone-regulated expression of &lt;i&gt;ERG&lt;/i&gt; persists in CRPC. [Cancer Res 2009;69(7):2912–8]&lt;/p&gt;&lt;/div&gt;