Pancreatic ductal adenocarcinoma (PDAC) is the seventh cause of death for cancer worldwide and the third in the USA, where it is expected to become the second by year 2030. Unlike other cancers, little progress has been made when it comes to therapeutic options other than surgery, which is possible only for a small fraction (~20%) of patients presenting with localised disease.1 2 For the above reasons, large efforts have been undertaken to get a deeper understanding of the molecular alterations and their effects on cancer cells and tumour microenvironment, by exploiting both innovative disease models and high-throughput studies for genomic and transcriptomic profiling of PDAC.3 4 In the meanwhile, genome-wide association studies, and the study of familial pancreatic cancer, have been looking for and found genetic variations associated to PDAC onset and outcome.5 6 At the genomic level, mutations in the coding region of several genes have been consistently identified, together with disruptive structural alterations whose effect has been linked to the altered functionality (eg, KRAS, TP53 ) or loss (eg, CDNK2A , SMAD4, ARID1A, ROBO2, BRCA1/2 ) of the respective gene products. Frequent and rare alterations identified converge in specific pathways, such as Wnt/Notch, Hedgehog, axon guidance, transforming growth factor beta, SWI/SNF (SWItch/sucrose non-fermentable) and DNA damage repair.3 RNA expression profiles, on the other …

中文翻译：

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非编码调控变异：胰腺癌基因组学的暗物质

一直在寻找并发现与 PDAC 发病和结果相关的遗传变异。 5 6 在基因组水平上，几个基因编码区的突变一直被确定，连同破坏性结构改变，其影响与功能改变有关（例如，KRAS、TP53）或相应基因产物的丢失（例如，CDNK2A、SMAD4、ARID1A、ROBO2、BRCA1/2）。发现的频繁和罕见的改变集中在特定途径中，例如 Wnt/Notch、Hedgehog、轴突导向、转化生长因子 β、SWI/SNF（SWITCH/蔗糖不可发酵）和 DNA 损伤修复。 3 RNA 表达谱，另一方面… 连同破坏性结构改变，其影响与相应基因产物的功能改变（例如，KRAS、TP53）或丢失（例如，CDNK2A、SMAD4、ARID1A、ROBO2、BRCA1/2）有关。发现的频繁和罕见的改变集中在特定途径中，例如 Wnt/Notch、Hedgehog、轴突导向、转化生长因子 β、SWI/SNF（SWITCH/蔗糖不可发酵）和 DNA 损伤修复。 3 RNA 表达谱，另一方面… 连同破坏性结构改变，其影响与相应基因产物的功能改变（例如，KRAS、TP53）或丢失（例如，CDNK2A、SMAD4、ARID1A、ROBO2、BRCA1/2）有关。发现的频繁和罕见的改变集中在特定途径中，例如 Wnt/Notch、Hedgehog、轴突导向、转化生长因子 β、SWI/SNF（SWITCH/蔗糖不可发酵）和 DNA 损伤修复。 3 RNA 表达谱，另一方面…