Subjects: Biology >> Biophysics >> Oncology submitted time 2016-05-11
Wu, Song
Duan, Li
Zhu, Weiming
Zhang, Shiquan
Yang, Guosheng
Liu, Chunxiao
Li, Weiping
Yang, Lei
Guo, Lijun
Wang, Yongqiang
He, Meijian
He, Yingying
Cai, Zhiming
Wang, Daping
Wu, Song
Liu, Hongjie
Hu, Xiaoxiao
Liu, Hongjie
Jia, Wenlong
Yang, Zhao
Abstract： Hereditary multiple exostosis (HME) is an autosomal inherited skeletal disease whose etiology is not fully understood. To further understand the genetic spectrum of the disease, we analyzed a five-generation Chinese family with HME that have observable inheritance. Exome sequencing was performed on three HME individuals and three unaffected individuals from the family. A downstream study confirmed a new C deletion at codon 442 on exon 5 of the exostosin-1 (EXT1) gene as the only pathogenic site which generated a stop codon and caused the truncation of the protein. We rediscovered the deletion in other affected individuals but not in the unaffected individuals from the family. Upon immunohistochemistry assay, we found that the EXT1 protein level of the patients with the novel mutation in our study was less than the level in the patients without the EXT1 mutation from another unrelated family. For a deeper understanding, we analyzed the mutation spectrum of the EXT1 gene. The present study should facilitate a further understanding of HME.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics >> Oncology submitted time 2016-05-11
Li, Chong
Yang, Zhao
Du, Ying
He, Luyun
Fan, Zusen
Li, Chong
Wu, Song
Cai, Zhiming
Wang, Haifeng
Wang, Jiansong
Bi, Xingang
Abstract： Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.
Peer Review Status:Awaiting Review
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