Department of Pathology, University of Virginia, Charlottesville, VA 22908, USA.
Lab Invest. 2011 Oct;91(10):1480-90. doi: 10.1038/labinvest.2011.105. Epub 2011 Jun 27.
Adenoid cystic carcinoma (ACC) is one of the most common malignancies to arise in human salivary glands, and it also arises in the glandular tissue of other organ systems. To address the paucity of experimental model systems for this tumor type, we have undertaken a program of transplanting tissue samples of human ACC into immunodeficient nu/nu mice to create xenograft model systems. In 17 of 23 attempts (74%), xenograft tumors were successfully grown. In all cases, the histologic appearance of the donating tumor was recapitulated in the subsequent xenograft. Characterization of a subset of xenograft models by immunohistochemical biomarkers and by RNA transcript microarray analysis showed good fidelity in the recapitulation of gene expression patterns in the xenograft tumors compared with the human donor tumors. As ACC is known to frequently contain a t(6;9) translocation that fuses the MYB and NFIB genes, fluorescence in situ hybridization (FISH) of 12 ACC xenograft models was performed that assayed MYB locus break-apart and MYB-NFIB locus fusion. Of 12 xenograft models, 11 (92%) revealed MYB locus rearrangement and 10 (83%) showed evidence of fusion of the MYB and NFIB loci. The two related xenograft models (derived from primary and metastatic tumors, respectively, of the same human subject) were karyotyped, showing a t(1;6) translocation, suggesting MYB translocation to a novel fusion partner gene. Overall, our results indicate that ACC is amenable to xenografting and that ACC xenograft models recapitulate the molecular and morphologic characteristics of human tumors, suggesting utility as valid experimental and preclinical model systems for this disease.
腺样囊性癌 (ACC) 是人类唾液腺中最常见的恶性肿瘤之一，也发生在其他器官系统的腺体组织中。为了解决这种肿瘤类型缺乏实验模型系统的问题，我们着手将人 ACC 的组织样本移植到免疫缺陷的 nu/nu 小鼠中，以创建异种移植模型系统。在 23 次尝试中的 17 次（74%），成功地生长了异种移植肿瘤。在所有情况下，供体肿瘤的组织学外观都在随后的异种移植中得到了重现。通过免疫组织化学生物标志物和 RNA 转录微阵列分析对一部分异种移植模型进行了表征，结果表明在异种移植肿瘤中重现基因表达模式的保真度很好，与人类供体肿瘤相比。由于已知 ACC 经常包含融合 MYB 和 NFIB 基因的 t(6;9)易位，因此对 12 种 ACC 异种移植模型进行了荧光原位杂交 (FISH) 检测，以检测 MYB 基因座断裂和 MYB-NFIB 基因座融合。在 12 种异种移植模型中，有 11 种（92%）显示 MYB 基因座重排，有 10 种（83%）显示 MYB 和 NFIB 基因座融合的证据。两个相关的异种移植模型（分别来自同一人类患者的原发性和转移性肿瘤）进行了染色体核型分析，显示 t(1;6)易位，提示 MYB 易位到一个新的融合伙伴基因。总的来说，我们的结果表明 ACC 适合异种移植，并且 ACC 异种移植模型重现了人类肿瘤的分子和形态特征，表明它们可用作该疾病的有效实验和临床前模型系统。
