INSERM, U842, Lyon, France.
Brain Pathol. 2011 Sep;21(5):533-43. doi: 10.1111/j.1750-3639.2011.00476.x. Epub 2011 Feb 23.
Integrative genomics approaches associating DNA structure and transcriptomic analysis should allow the identification of cascades of events relating to tumor aggressiveness. While different genome alterations have been identified in pituitary tumors, none have ever been correlated with the aggressiveness. This study focused on one subtype of pituitary tumor, the prolactin (PRL) pituitary tumors, to identify molecular events associated with the aggressive and malignant phenotypes. We combined a comparative genomic hybridization and transcriptomic analysis of 13 PRL tumors classified as nonaggressive or aggressive. Allelic loss within the p arm region of chromosome 11 was detected in five of the aggressive tumors. Allelic loss in the 11q arm was observed in three of these five tumors, all three of which were considered as malignant based on the occurrence of metastases. Comparison of genomic and transcriptomic data showed that allelic loss impacted upon the expression of genes located in the imbalanced region. Data filtering allowed us to highlight five deregulated genes (DGKZ, CD44, TSG101, GTF2H1, HTATIP2), within the missing 11p region, potentially responsible for triggering the aggressive and malignant phenotypes of PRL tumors. Our combined genomic and transcriptomic analysis underlines the importance of chromosome allelic loss in determining the aggressiveness and malignancy of tumors.
综合基因组学方法将 DNA 结构与转录组分析相结合，应该能够鉴定与肿瘤侵袭性相关的级联事件。虽然已经在垂体肿瘤中鉴定出了不同的基因组改变，但没有一种与侵袭性相关。本研究集中在垂体肿瘤的一种亚型，即催乳素（PRL）垂体肿瘤，以鉴定与侵袭性和恶性表型相关的分子事件。我们对 13 例被归类为非侵袭性或侵袭性的 PRL 肿瘤进行了比较基因组杂交和转录组分析。在 5 例侵袭性肿瘤中检测到 11 号染色体 p 臂区域的等位基因丢失。在这 5 例肿瘤中有 3 例观察到 11q 臂的等位基因丢失，所有这 3 例均根据转移的发生被认为是恶性的。基因组和转录组数据的比较表明，等位基因丢失影响位于不平衡区域的基因的表达。数据筛选使我们能够突出 5 个失调基因（DGKZ、CD44、TSG101、GTF2H1、HTATIP2），这些基因位于缺失的 11p 区域内，可能导致 PRL 肿瘤的侵袭性和恶性表型。我们的综合基因组学和转录组学分析强调了染色体等位基因丢失在决定肿瘤侵袭性和恶性程度方面的重要性。
