Hurst Carolyn D, Alder Olivia, Platt Fiona M, Droop Alastair, Stead Lucy F, Burns Julie E, Burghel George J, Jain Sunjay, Klimczak Leszek J, Lindsay Helen, Roulson Jo-An, Taylor Claire F, Thygesen Helene, Cameron Angus J, Ridley Anne J, Mott Helen R, Gordenin Dmitry A, Knowles Margaret A
Section of Molecular Oncology, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Cancer Research UK Leeds Centre, Leeds Institute of Cancer and Pathology, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.
Cancer Cell. 2017 Nov 13;32(5):701-715.e7. doi: 10.1016/j.ccell.2017.08.005.
Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes. More mutations in the histone lysine demethylase KDM6A were present in non-invasive tumors from females than males.
由于非侵袭性疾病频繁复发，膀胱癌的终身治疗成本高于其他癌症。对于这个庞大的患者群体，需要改进预后生物标志物和局部治疗方法。我们定义了原发性Ta期肿瘤的两种主要基因组亚型。其中一种亚型的特征是9号染色体长臂缺失，包括TSC1基因，KI67标记指数增加，糖酵解、DNA修复、mTORC1信号上调，未折叠蛋白反应特征以及胆固醇稳态改变。与肌层浸润性膀胱癌的突变谱比较显示，总体突变率较低，RHOB基因和染色质修饰基因的突变更为频繁。女性非侵袭性肿瘤中组蛋白赖氨酸去甲基化酶KDM6A的突变比男性更多。
