公开(公告)号：EP1259628A1

公开(公告)日：2002-11-27

申请号：EP01911013.9

申请日：2001-02-21

申请人： The Johns Hopkins UNiversity School of Medicine ,  Nicolaides, Nicholas, C. ,  Sass, Philip, M. ,  Grasso, Luigi ,  Vogelstein, Bert ,  Kinzler, Kenneth

发明人： NICOLAIDES, Nicholas, C. ,  SASS, Philip, M. ,  GRASSO, Luigi ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/81 ,  C12N5/10 ,  C12N15/01

CPC分类号： C12N15/81

摘要： Yeast cells are mutagenized to obtain desirable mutants. Mutagenesis is mediated by a defective mismatch repair system which can be enhanced using conventional exogenously applied mutagens. Yeast cells with the defective mismatch repair system are hypermutable, but after selection of desired mutant yeast strains, they can be rendered genetically stable by restoring the mismatch repair system to proper functionality.

公开(公告)号：EP1220952A2

公开(公告)日：2002-07-10

申请号：EP00968746.8

申请日：2000-10-06

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  YAN, Hai ,  PAPADOPOULOS, Nicholas

IPC分类号： C12Q1/68 ,  C12N15/06 ,  C12N5/26

CPC分类号： C12N5/166 ,  C12Q1/6886 ,  C12Q2600/156

摘要： Detection of mutations associated with hereditary diseases is complicated by the diploid nature of mammalian cells. Mutations present in one allele are often masked by the wild-type sequence of the other allele. Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion. Nucleic acids from the hybrids can be analyzed for mutations in an unambiguous manner. This approach was used to detect two cancer-causing mutations that had previously defied genetic diagnosis. One of the families studied, Warthin Family G, was the first kindred with a hereditary colon cancer syndrome described in the biomedical literature.

公开(公告)号：EP1133573A2

公开(公告)日：2001-09-19

申请号：EP99960522.3

申请日：1999-11-22

申请人： The Johns Hopkins University

发明人： LAKEN, Steven, J. ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  GROOPMAN, John, D. ,  JACKSON, Peta, E. ,  FRIESEN, Marlin, D.

IPC分类号： C12Q1/68 ,  G01N30/72 ,  G01N33/50

CPC分类号： C12Q1/683 ,  C12Q1/6844 ,  C12Q1/6872 ,  C12Q2565/627 ,  C12Q2525/204 ,  C12Q2521/313 ,  C12Q2525/131

摘要： Genotyping can be accomplished by analysis of short, defined DNA segments using electrospray ionization mass spectrometry. The DNA segments are produced using specially designed primers to amplify a cDNA or genomic DNA template. The primers contain a recognition site for a restriction endonuclease. The amplification products are digested with the restriction endonuclease. Single nucleotide polymorphisms can be detected rapidly and reliably.

摘要翻译： 基因分型可以通过使用电喷雾电离质谱法分析短的，确定的DNA片段来完成。 使用特别设计的引物来产生DNA片段以扩增cDNA或基因组DNA模板。 引物含有限制性内切核酸酶的识别位点。 扩增产物用限制性内切酶消化。 单核苷酸多态性可以快速可靠地检测到。

公开(公告)号：EP0970202A2

公开(公告)日：2000-01-12

申请号：EP98902680.2

申请日：1998-01-22

申请人： THE JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE

发明人： VELCULESCU, Victor E. ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth, W.

IPC分类号： C12N15/10 ,  C12N15/31 ,  C07K14/395 ,  C12Q1/68 ,  C12Q1/02

CPC分类号： C07K14/395

摘要： Yeast genes which are differentially expressed during the cell cycle are described. They can be used to study, affect, and monitor the cell cycle of a eukaryotic cell. They can be used to obtain human homologs involved in cell cycle regulation. They can be used to identify antifungal agents. They can be formed into arrays on solid supports for interrogation of a cell's transcriptome under various conditions.

公开(公告)号：EP3907299A1

公开(公告)日：2021-11-10

申请号：EP21173115.3

申请日：2012-04-12

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth ,  PAPADOPOULOS, Nickolas ,  KINDE, Isaac

IPC分类号： C12Q1/6874 ,  C12N15/11 ,  C12Q1/6806

摘要： The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called "Safe-SeqS" for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant ("super-mutants") if =95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.

公开(公告)号：EP2956556B1

公开(公告)日：2019-04-10

申请号：EP14751900.3

申请日：2014-02-18

申请人： Duke University ,  The Johns Hopkins University

发明人： YAN, Hai ,  VOGELSTEIN, Bert ,  PAPADOPOULOS, Nickolas ,  KINZLER, Kenneth W. ,  JIAO, Yuchen ,  BETTEGOWDA, Chetan ,  BIGNER, Darell D.

IPC分类号： C12Q1/6886

公开(公告)号：EP3322824A1

公开(公告)日：2018-05-23

申请号：EP16825025.6

申请日：2016-07-12

申请人： The Johns Hopkins University

发明人： BETTEGOWDA, Chetan ,  KINZLER, Kenneth W. ,  VOGELSTEIN, Bert ,  WANG, Yuxuan ,  DIAZ, Luis ,  PAPADOPOULOS, Nickolas

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/156

摘要： As cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we assessed the cerebrospinal fluid (CSF) that bathes the CNS for tumor DNA, here termed CSF-tDNA. The results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

公开(公告)号：EP3266879A1

公开(公告)日：2018-01-10

申请号：EP17168866.6

申请日：2009-09-03

申请人： The Johns Hopkins University ,  Duke University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth ,  PAPADOPOULOS, Nickolas ,  VELCULESCU, Victor ,  PARMIGIANI, Giovanni ,  KARCHIN, Rachel ,  JONES, Sian ,  YAN, Hai ,  BIGNER, Darell ,  KUAN, Chien-Tsun ,  RIGGINS, Gregory ,  PARSONS, Williams ,  ZHANG, Xiaosong ,  LIN, Jimmy Cheng-Ho ,  LEARY, Rebecca ,  ANGENENDT, Philipp

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136 ,  C12Q2600/156

摘要： We found mutations of the R132 residue of isocitrate dehydrogenase 1 (IDH1) in the majority of grade II and III astrocytomas and oligodendrogliomas as well as in glioblastomas that develop from these lower grade lesions. Those tumors without mutations in IDH1 often had mutations at the analogous R172 residue of the closely related IDH2 gene. These findings have important implications for the pathogenesis and diagnosis of malignant gliomas.

摘要翻译： 我们在大多数II级和III级星形细胞瘤以及少突胶质细胞瘤以及从这些低级病变发展而来的胶质母细胞瘤中发现异柠檬酸脱氢酶1（IDH1）的R132残基突变。 没有IDH1突变的那些肿瘤通常在密切相关的IDH2基因的类似R172残基处具有突变。 这些发现对于恶性神经胶质瘤的发病机制和诊断具有重要意义。

公开(公告)号：EP2315849B1

公开(公告)日：2017-11-08

申请号：EP09803662.7

申请日：2009-07-31

申请人： The Johns Hopkins University

发明人： DIEHL, Frank ,  DIAZ, Luis ,  KINZLER, Kenneth, W. ,  VOGELSTEIN, Bert ,  SCHMIDT, Kerstin

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6886 ,  C12Q2525/197 ,  C12Q2535/131 ,  C12Q2549/119 ,  C12Q2600/112 ,  C12Q2600/118 ,  C12Q2600/136

公开(公告)号：EP2726869B1

公开(公告)日：2017-08-09

申请号：EP12804757.8

申请日：2012-06-28

申请人： Duke University ,  The Johns Hopkins University

发明人： YAN, Hai ,  BIGNER, Darell ,  VOGELSTEIN, Bert ,  KINZLER, Kenneth W. ,  MEEKER, Alan ,  HRUBAN, Ralph ,  PAPADAPOULOS, Nickolas ,  DIAZ, Luis ,  JIAO, Yuchen

IPC分类号： G01N33/53 ,  C12Q1/68 ,  A61K39/00 ,  A61K31/7105

CPC分类号： C12Q1/6886 ,  C07K16/40 ,  C12N15/1137 ,  C12Q2600/118 ,  C12Q2600/156 ,  G01N33/57407

摘要： We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.

摘要翻译： 我们在来自不同地点的447种癌症中确定了ATRX和DAXX的序列。 我们发现小儿胶质母细胞瘤多形性（GBM）（11.1％），成人GBM（6.5％），少突胶质细胞瘤（7.7％）和成神经管细胞瘤（1.5％）中最常见突变; 并表明端粒替代延长（ALT）是一种端粒酶非依赖性端粒维持机制，在未激活端粒酶的癌症中发现，与任一基因的体细胞突变完全相关。 相反，神经母细胞瘤和卵巢癌，乳腺癌和胰腺腺癌的ATRX和DAXX突变均为阴性。 ATRX或DAXX的改变定义了与人类癌症中替代的端粒维持功能密切相关的特定分子途径。