Novel variants inMLLconfer to bladder cancer recurrence identified by whole-exome sequencing

• DOI: 10.18632/oncotarget.6380
• Publication Date: 2015-11-26T16:21:37Z
• Authors: Song Wu; Zhao Yang; Rui Ye; Dan An; Chong Li; Yitian Wang; Yongqiang Wang; Yi Huang; Huan Liu; Feida Li; Luyun He; Da Sun; Yuan Yu; Qiaoling Li; Peide Huang; Meng Zhang; Xin Zhao; Tengteng Bi; Xuehan Zhuang; Liyan Zhang; Jingxiao Lu; Xiaojuan Sun; Fangjian Zhou; Chunxiao Liu; Guosheng Yang; Yong Hou; Zusen Fan; Zhiming Cai
• Keywords: Epirubicin; Exome; H3K4me3

// Song Wu 1,4,* , Zhao Yang 2,3,* Rui Ye 5,* Dan An Chong Li 2,* Yitian Wang 4,6,* Yongqiang 7 Yi Huang 4 Huan Liu 5 Feida Luyun He 2 Da Sun Yuan Yu Qiaoling Peide Meng Zhang 6 Xin Tengteng Bi Xuehan Zhuang Liyan Jingxiao Lu Xiaojuan Fangjian Zhou Chunxiao 8 Guosheng 9 Yong Hou Zusen Fan and Zhiming Cai 4,6 1 The Affiliated Luohu Hospital of Shenzhen University, Group, Shenzhen, China CAS Key Laboratory Infection Immunity, Institute Biophysics, Chinese Academy Sciences, Beijing, 3 Pathogenic Microbiology Immunology, Microbiology, Department Urological Surgery, Second People's Hospital, First BGI-Shenzhen, Anhui Medical Hefei, Urology, Yat-sen University Cancer Center, Guangzhou, Zhujiang Southern Guangdong * These authors have contributed equally to this work Correspondence to: Cai, email: Fan, Keywords : bladder cancer, tumor recurrence, MLL, drug-resistance, whole-exome sequencing Received May 27, 2015 Accepted October 14, Published November 25, Abstract Bladder cancer (BC) is distinguished by high rate recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed 37 BC individuals including 20 primary 17 recurrent samples in which were not from same patient. We uncovered that MLL EP400 PRDM2 ANK3 CHD5 exclusively altered BCs. Specifically, BCs cells with mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification tissue cell levels showed enhanced expression GATA4 ETS1 downstream. What's more, mutated obtained CRISPR/Cas9 ability drug-resistance epirubicin (a chemotherapy drug for cancer) than wild type cells. Additionally, patients significantly shorter lifespan low expression. Our study provided an overview genetic basis recrudescent discovered alterations involved relapse. H3K4me3 would be promising targets diagnosis therapy relapsed cancer.