Topham James T, Karasinska Joanna M, Metcalfe Andrew, Ali Hassan A, Kalloger Steve E, Kevorkova Maya, Titmuss Emma, Negri Gian Luca, Spencer Sandra E, Jang Gun Ho, O'Kane Grainne M, Moore Richard A, Mungall Andrew J, Loree Jonathan M, Notta Faiyaz, Wilson Julie M, Bathe Oliver F, Tang Patricia A, Goodwin Rachel, Morin Gregg B, Knox Jennifer J, Gallinger Steven, Laskin Janessa, Marra Marco A, Jones Steven J M, Renouf Daniel J, Schaeffer David F
Pancreas Centre BC, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, UBC, Vancouver, BC, Canada.
iScience. 2025 Jul 22;28(8):113176. doi: 10.1016/j.isci.2025.113176. eCollection 2025 Aug 15.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. While genome profiling has benefitted clinical decision-making in many cancer types, PDAC remains among the most lethal solid cancers and has relatively few clinically actionable molecular targets. Using a multi-omics approach, we integrate whole-genome and transcriptome datasets along with proteomics and clinical metadata to identify copy-altered regions with significant impact on expression at the whole-genome scale. This approach identified and as focally amplified and over-expressed genes located on chr7q21/22 with expression negatively correlated with patient survival. We extrapolate these results into a pan-cancer analysis to demonstrate that the association between amplification versus expression is strongest in PDAC among 23 other cancer types. Taken together, these data provide a detailed overview of the copy number landscape in PDAC while highlighting chr7q21/22 amplification as a recurrent somatic event impacting both gene expression and patient survival.
胰腺导管腺癌（PDAC）是一种侵袭性很强的疾病，治疗选择有限。虽然基因组分析在许多癌症类型中有助于临床决策，但PDAC仍然是最致命的实体癌之一，临床上可操作的分子靶点相对较少。我们采用多组学方法，整合全基因组和转录组数据集以及蛋白质组学和临床元数据，以在全基因组规模上识别对表达有重大影响的拷贝改变区域。该方法确定了位于7号染色体q21/22上的 和 为局灶性扩增和过表达基因，其表达与患者生存率呈负相关。我们将这些结果外推到泛癌分析中，以证明在23种其他癌症类型中， 扩增与表达之间的关联在PDAC中最为显著。综上所述，这些数据提供了PDAC中拷贝数格局的详细概述，同时突出了7号染色体q21/22扩增是影响基因表达和患者生存的复发性体细胞事件。
