PDF(Pubmed)
Abstract：
3\'UTR-APAs have been extensively studied, but intronic polyadenylations (IPAs) remain largely unexplored. We characterized the profiles of 22 260 IPAs in 9679 patient samples across 32 cancer types from the Cancer Genome Atlas cohort. By comparing tumor and paired normal tissues, we identified 180 ~ 4645 dysregulated IPAs in 132 ~ 2249 genes in each of 690 patient tumors from 22 cancer types that showed consistent patterns within individual cancer types. We selected 2741 genes that showed consistently patterns across cancer types, including 1834 pan-cancer tumor-enriched and 907 tumor-depleted IPA genes; the former were amply represented in the functional pathways such as deoxyribonucleic acid damage repair. Expression of IPA isoforms was associated with tumor mutation burden and patient characteristics (e.g. sex, race, cancer stages, and subtypes) in cancer-specific and feature-specific manners, and could be a more accurate prognostic marker than gene expression (summary of all isoforms). In summary, our study reveals the roles and the clinical relevance of tumor-associated IPAs.
摘要：
3个UTR-APA已经被广泛研究，但是内含子多腺苷酸化（IPA）仍未被探索。我们对来自癌症基因组图谱队列的32种癌症类型的9679例患者样本中的22.260IPA进行了表征。通过比较肿瘤和配对的正常组织，我们在来自22种癌症类型的690例患者肿瘤中的132~2249个基因中的每个基因中鉴定出180~4645个异常调节的IPA,这些肿瘤在单个癌症类型中显示出一致的模式.我们选择了2741个基因，这些基因在癌症类型中表现出一致的模式，包括1834个泛癌症肿瘤富集和907个肿瘤耗尽的IPA基因；前者在脱氧核糖核酸损伤修复等功能途径中得到充分代表。IPA亚型的表达与肿瘤突变负荷和患者特征(例如性别、种族,癌症阶段，和亚型)以癌症特异性和特征特异性的方式，并且可能是比基因表达更准确的预后标志物（所有亚型的摘要）。总之,我们的研究揭示了肿瘤相关IPA的作用和临床意义.
