Laboratorio Nacional de Genómica para la Biodiversidad, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Irapuato, Guanajuato, México.
PLoS One. 2010 May 3;5(5):e10398. doi: 10.1371/journal.pone.0010398.
A central goal of cancer biology is to understand how cells from this family of genetic diseases undergo specific morphological and physiological changes and regress to a de-regulated state of the cell cycle. The fact that tumors are unable to perform most of the specific functions of the original tissue led us to hypothesize that the degree of specialization of the transcriptome of cancerous tissues must be less than their normal counterparts. With the aid of information theory tools, we analyzed four datasets derived from transcriptomes of normal and tumor tissues to quantitatively test the hypothesis that cancer reduces transcriptome specialization. Here, we show that the transcriptional specialization of a tumor is significantly less than the corresponding normal tissue and comparable with the specialization of dedifferentiated embryonic stem cells. Furthermore, we demonstrate that the drop in specialization in cancerous tissues is largely due to a decrease in expression of genes that are highly specific to the normal organ. This approach gives us a better understanding of carcinogenesis and offers new tools for the identification of genes that are highly influential in cancer progression.
癌症生物学的一个核心目标是了解这些遗传疾病的细胞如何发生特定的形态和生理变化，并回归到细胞周期的失调状态。事实上，肿瘤无法执行原始组织的大多数特定功能，这使我们假设癌组织转录组的专业化程度必须低于其正常对应物。借助信息论工具，我们分析了来自正常和肿瘤组织转录组的四个数据集，以定量测试癌症降低转录组专业化的假设。在这里，我们表明肿瘤的转录专业化明显低于相应的正常组织，与去分化的胚胎干细胞的专业化相当。此外，我们证明，癌组织中专业化程度的下降在很大程度上是由于对正常器官高度特异的基因表达降低所致。这种方法使我们对癌症发生有了更好的理解，并为鉴定在癌症进展中具有高度影响力的基因提供了新的工具。
