收藏本站
收藏 | 手机打开
二维码
手机客户端打开本文

SETD8C302R mutation revealed from myofibroblastoma-discordant monozygotic twins leads to p53/p21 deficit and WEE1 inhibitor sensitivity

Li Miao  Wang Hongwu  Liao Hongwei  Shen Jiaxin  Wu Yinfang  Wu Yanping  Weng Qingyu  Zhu Chen  Geng Xinwei  Lan Fen  Xia Yang  Zhang Bin  Zou Heng  Zhang Nan  Zhou Yunzhi  Chen Zhihua  Shen Huahao  Ying Songmin  Li Wen  
【摘要】:Objective Background High-throughput gene sequencing have identified a number of common genetic variants as the culprits for some cancers of high incidence, facilitating the development of targeted therapeutics. In contrast, rare deleterious mutations are much less understood because they are hidden in a myriad of nonsense genetic variations, which poses great challenge to the understanding of the pathology and thus the rational design of effective treatments for affected patients. Methods Germline DNA from a pair of monozygotic(MZ) twins discordant for lung inflammatory myofibroblastoma(IMT) were sequenced. With the healthy twin sister and the 1,000 genomes as the reference, candidate pathogenic mutations in the patient were screened out from the rare and potentially deleterious variants on the basis of the enrichment score. Promising candidates were further subjected to functional validation and therapeutic targeting evaluation. Results We identified a missense single nucleotide variation rs61955126 TC in the lysine methyltransferase SETD8(Accession: NM_020382, SETD8 C302 R) from the patient. In functional studies, we demonstrated that SETD8 was required for faithful DNA replication and genomic integrity, and its C302 R mutation downregulated the p53/21 pathway. Importantly, The SETD8 C302 R mutation conferred hypersensitivity of cancer cells to WEE1 inhibition. Conclusion Whole genome sequencing on monozygotic twins provides a unique opportunity for interrogating rare pathogenetic mutations. Using this strategy, we identified a rare mutation of SETD8(SETD8 C302 R), and unraveled its role in genome stability maintenance. Particularly, we revealed that cancer cells carrying SETD8 C302 R may be effectively treated by WEE1 inhibitor that is already under clinical trials.

知网文化
【相似文献】
中国期刊全文数据库 前20条
1 LIU Qiu Yu;KONG Ling Fei;XU Zi Gung;LI Zhen;XUE Huan Zhou;;Mutation of the KIT Gene, excluding Exon 11, in Gastrointestinal Stromal Tumors[J];Biomedical and Environmental Sciences;2020年05期
2 吕成兰;;The impact of meisoindigo on apoptosis and proliferation of SET2 cell line by JAK-STAT pathway[J];China Medical Abstracts(Internal Medicine);2019年02期
3 Rong Gao;Wei Gao;Gang Xu;Jie Xu;Hao Ren;;Single amino acid mutation of SR-BI decreases infectivity of hepatitis C virus derived from cell culture in a cell culture model[J];World Journal of Gastroenterology;2017年28期
4 杨长绍;;Mutation status of epidermal growth factor receptor and KRAS gene in non-small cell long cancers at Xuanwei regions of Yunnan Province[J];China Medical Abstracts(Internal Medicine);2016年02期
5 Ofer Isakov;Dorit Lev;Lubov Blumkin;Gershon Celniker;Esther Leshinsky-Silver;Noam Shomron;;Crowdfunding Effort Identifies the Causative Mutation in a Patient with Nystagmus,Microcephaly,Dystonia and Hypomyelination[J];Journal of Genetics and Genomics;2015年02期
6 ;About the Cover[J];Chinese Journal of Cancer;2015年10期
7 杨向绸;;SRSF2 mutation in patients with chronic myelomonocytic leukemia[J];China Medical Abstracts(Internal Medicine);2014年01期
8 彭雪清;;浅谈农村合作社的“异变”On rural cooperatives “mutation”[J];商;2014年19期
9 ;Establishment of Rapid Propagation System for Saponaria officinalis L. Progeny After EMS Mutation[J];Journal of Northeast Agricultural University(English Edition);2012年01期
10 邵春燕;路艳;刘谟焓;陈琪;蓝云峰;刘岩;林敏;李泱;;Electrophysiological Study of V535M hERG Mutation of LQT2[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2011年06期
11 乔建坤;王涛;杨俊;刘继红;龚小新;郭小林;王少刚;叶章群;;Genetic Mutation of Vitamin K-dependent Gamma-glutamyl Carboxylase Domain in Patients with Calcium Oxalate Urolithiasis[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2009年05期
12 ;Mutation analysis of PAX6 gene in a large Chinese family with aniridia[J];Chinese Medical Journal;2005年04期
13 YEUNG Wai Lan,LAM Ching Wan,CHENG Wai Tsoi,SIN Ngai Chuen,WONG Wing Kin,WONG Chun Nei,TSE Ka Ming,FOK Tai Fai;Early-onset primary torsional dystonia in a 4-generation Chinese family with a mutation in the DYT1 gene[J];Chinese Medical Journal;2005年10期
14 李敏伟,侯伟,沃健儿,刘克洲;Character of HBV (hepatitis B virus) polymerase gene rtM204V/I and rtL180M mutation in patients with lamivudine resistance[J];Journal of Zhejiang University Science;2005年07期
15 崔文;吴仁亮;曹慧玲;高继发;王旭;任启伟;;P53 Gene Mutation and Expression of MDM2, P53,P16 Protein and their Relationship in Human Glioma[J];华中科技大学学报(医学英德文版);2005年06期
16 邵世煌,肖绚,丁永生,黄振德;Visualization of Gene Mutation Complicated Pattern of Hepatitis B Virus Based on Cellular Automata[J];Journal of DongHua University;2005年01期
17 林青雲,陳安琪,赖志刚,陳偉雄,陳恩和,石志忠,湯瑞芬;A novel mutation, Y255X, of the ARSB gene in a Chinese family with mucopolysaccharidosis type Ⅵ[J];Chinese Medical Journal;2004年12期
18 滕云,田虹,王慧,胡晓峰,王嵬,陈燕,杨真荣;Mutation Identification in A 5-Generation Pedigree with Autosomal Dominant Retinitis Pigmentosa[J];华中科技大学学报(医学英德文版);2003年03期
19 孙野青 ,魏力军 ,李小乐 ,赵海成 ,辛平 ,关双红;Rice mutation after flown in space[J];Journal of Harbin Institute of Technology;2002年01期
20 丁国宪 ,沈捷 ,陈家伟;Relationship between the Mutation of IRS-1 Gene and β_3-adrenergic Receptor Gene[J];Journal of Nanjing Medical University;2001年02期
中国重要会议论文全文数据库 前20条
1 吴喜萍;王海峰;;Rare genetic E196A mutation in patient with Creutzfeldt-Jacob disease:a case report and literature[A];2020年浙江省神经病学学术大会论文汇编[C];2020年
2 Li Miao;Wang Hongwu;Liao Hongwei;Shen Jiaxin;Wu Yinfang;Wu Yanping;Weng Qingyu;Zhu Chen;Geng Xinwei;Lan Fen;Xia Yang;Zhang Bin;Zou Heng;Zhang Nan;Zhou Yunzhi;Chen Zhihua;Shen Huahao;Ying Songmin;Li Wen;;SETD8C302R mutation revealed from myofibroblastoma-discordant monozygotic twins leads to p53/p21 deficit and WEE1 inhibitor sensitivity[A];2020年(第四十二届)浙江省医学会呼吸系病学术大会论文汇编[C];2020年
3 Peng Wang;Tingting Qu;Yuanyuan Qu;Xiaojing Kang;;Pan-cancer analysis of the oncogenic role of PLCG2 gene in human tumors[A];2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛论文集[C];2021年
4 Jiayu Zhang;Ting Yang;Mei Han;Xiaoxuan Wang;Xin Zhai;Chunfu Wu;Lihui Wang;;The gain-of-function mutation in DOT1L promotes lung cancer tumorigenesis and induces drug resistance via the MAPK/ERK signaling pathway[A];2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛论文集[C];2021年
5 Qiaomei Guo;Xia Ahung;Mingna Zhao;Mengyan Wang;Jiatao Lou;;Comparative analysis of QS3D and droplet digital PCR for detection of plasma EGFR T790M mutation at disease progression[A];2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛论文集[C];2021年
6 SHI Yan jun;ZHANG Chun mei;GUO Hong ge;Yang Hai bin;Shen Jing ru;;Combination mutation strategy and parameter adaptive differential evolution algorithm[A];第31届中国过程控制会议(CPCC 2020)摘要集[C];2020年
7 Chunmei Zhang;Jingru Shen;Jie Hao;;Green Logistics Vehicle Path Optimization Based on Hybrid Discrete Differential Evolution Algorithm[A];第32届中国控制与决策会议论文集(5)[C];2020年
8 Xingyu Cui;Huifeng Zhang;Jiawei He;;Multi-subpopulation coevolutionary algorithm with adaptive Cauchy-Polynomial mutation[A];第40届中国控制会议论文集(3)[C];2021年
9 Tianwen Ding;Jingqi Fu;Renliang Shen;;Research on Multidimensional Mutation Strategy Method of Fuzzing Test[A];第40届中国控制会议论文集(15)[C];2021年
10 Yu Xue;Yi Liu;Wenjing Li;Na Zhao;Qiuhong Xiong;Ping Li;Kang Chen;Changxin Wu;Yanling Yang;Han Xiao;;Novel de novo mutation in the autophagy gene WDR45 cause BPAN in a Chinese family[A];2018中国遗传学会第十次全国会员代表大会暨学术讨论会论文摘要汇编[C];2018年
11 Fei Jia;Ren Li;Zewen Wei;Zhiyuan Hu;;A microfluidic chip for co-mutation detection in clinical samples at single-cell level[A];2019年中国肿瘤标志物学术大会暨第十三届肿瘤标志物青年科学家论坛论文集[C];2019年
12 吕慧芳;聂彩云;陈贝贝;韩黎丽;别良玉;侯宏霖;陈小兵;;PIK3CA and TP53 Mutation and its Correlation with Immune Signaling Pathway of Gastric Cancer[A];2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛论文集[C];2018年
13 徐君南;孙涛;;Elevated tumor mutation burden and immunogenic activity in patients with hormone receptor-negative or HER2-positive breast cancer[A];2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛论文集[C];2018年
14 张兴;付雨农;顾静娴;苗润晨;项晓烘;马小华;曲凯;刘昌;;Low expression of P2RX7 can play as a diagnostic marker in ICC with IDH1R132C mutation: evidence from comprehensive mutation profiling and pathway enrichment analysis[A];2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛论文集[C];2018年
15 QiaomeiGuo;Lin Wang;Wenjun Yu;PeijunZhai;Jiatao Lou;;Evaluation of the performance of EGFR mutations detection in advanced NSCLC patientswith droplet digital PCR[A];2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛论文汇编[C];2017年
16 Yanfen Feng;Yiyan Lei;Xiaoyan Wu;Yuhua Huang;Huilan Rao;Yu Zhang;Fang Wang;;GTF2I mutation occurs frequently in more indolent thymic epithelial tumors and predicts better prognosis[A];2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛论文汇编[C];2017年
17 Qiao-mei Guo;Lin Wang;Yun-hua Xu;Wen-jun Yu;Li-hua Qiao;Ming-na Zhao;Chen-zi Zhang;Xiao-meng Hu;Sheng Ni;Jia-tao Lou;;Evaluation of the performance for EGFR mutations detection in ctDNA from advanced NSCLC patients with droplet digital PCR[A];2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛论文汇编[C];2017年
18 GUO Yibin;PAN Jingxin;GUO Dongwei;XIE Jie;FANG Zishui;AI Yang;LI Rong;JIANG Yu;JIANG Weiying;FANG Qun;GUO Chunmiao;;The prenatal diagnosis of high risk fetus with severe short limb malformation and a preliminary study on the high incidence mutation and homozygous mutation mechanism of R248C of TD-I type[A];中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会论文汇编[C];2016年
19 党玉洁;唐蓉;陈子江;;WNT9B gene in 542 Chinese women with Mullerian Duct Abnormalities:mutation analysis[A];中华医学会第六次全国生殖医学学术会议专刊[C];2012年
20 Guang-jian Liu;Ying Fang;Jian-hua Wu;;The Dynamics Changes of vWF A1 Domain Induced by Gain-of-function Mutation[A];第十届全国生物力学学术会议暨第十二届全国生物流变学学术会议论文摘要汇编[C];2012年
中国硕士学位论文全文数据库 前8条
1 王佳;三角范畴中corigid子范畴的mutation[D];湘潭大学;2021年
2 伍三叶;三角范畴中的Mutation[D];湖南师范大学;2015年
3 耿圣飞;2-有限图的分类[D];四川大学;2007年
4 山晓东;关于skein树的一些性质[D];大连理工大学;2009年
5 阿育(AYU SEPTI ANGGRAENI);[D];华中农业大学;2013年
6 林伟森;桉树基因测序数据SNP的模式识别方法的研究[D];华南农业大学;2016年
7 吴婷;雄激素不敏感综合征10例临床与遗传学分析[D];重庆医科大学;2021年
8 李焕;MMP-9基因在河南汉族颅内动脉瘤患者中的突变[D];郑州大学;2020年
 快捷付款方式  订购知网充值卡  订购热线  帮助中心
  • 400-819-9993
  • 010-62982499
  • 010-62783978