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：EP2326735A1

公开(公告)日：2011-06-01

申请号：EP09792198.5

申请日：2009-09-03

申请人： The Johns Hopkins University ,  Duke University

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

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.

公开(公告)号：EP3266879B1

公开(公告)日：2019-07-03

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

公开(公告)号：EP2326735B1

公开(公告)日：2016-11-16

申请号：EP09792198.5

申请日：2009-09-03

申请人： The Johns Hopkins University ,  Duke University

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

IPC分类号： C12Q1/68

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

公开(公告)号：EP2326734B1

公开(公告)日：2016-11-09

申请号：EP09812193.2

申请日：2009-09-03

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  PARSONS, Donald William ,  JONES, Sian ,  ZHANG, Xiaosong ,  LIN, Jimmy Chang-Ho ,  LEARY, Rebecca J. ,  ANGENENDT, Philipp ,  PAPADOPOULOS, Nickolas ,  VELCULESCU, Victor ,  PARMIGIANI, Giovanni ,  KARCHIN, Rachel ,  KERN, Scott ,  HRUBAN, Ralph ,  ESHLEMAN, James R. ,  GOGGINS, Michael ,  KLEIN, Alison

IPC分类号： C12Q1/68

CPC分类号： G01N33/57438 ,  C12Q1/6886 ,  C12Q2600/156 ,  G01N2800/50

公开(公告)号：EP2326734A2

公开(公告)日：2011-06-01

申请号：EP09812193.2

申请日：2009-09-03

申请人： The Johns Hopkins University

发明人： VOGELSTEIN, Bert ,  KINZLER, Kenneth, W. ,  PARSONS, D., Williams ,  JONES, Sian ,  ZHANG, Xiaosong ,  LIN, Jimmy Chang-Ho ,  LEARY, Rebecca J. ,  ANGENENDT, Philipp ,  PAPADOPOULOS, Nickolas ,  VELCULESCU, Victor ,  PARMIGIANI, Giovanni ,  KARCHIN, Rachel ,  KERN, Scott ,  HRUBAN, Ralph ,  ESHLEMAN, James R. ,  GOGGINS, Michael ,  KLEIN, Alison

IPC分类号： C12Q1/68

CPC分类号： G01N33/57438 ,  C12Q1/6886 ,  C12Q2600/156 ,  G01N2800/50

摘要： There are currently few therapeutic options for patients with pancreatic cancers and new insights into the pathogenesis of this lethal disease are urgently needed. To this end, we performed a comprehensive analysis of the genes altered in 24 pancreatic tumors. First, we determined the sequences of 23,781 transcripts, representing 20,583 protein-encoding genes, in DNA from these tumors. Second, we searched for homozygous deletions and amplifications using microarrays querying ~one million single nucleotide polymorphisms in each sample. Third, we analyzed the transcriptomes of the same samples using SAGE and next-generation sequencing-by-synthesis technologies. We found that pancreatic cancers contain an average of 63 genetic alterations, of which 49 are point mutations, 8 are homozygous deletions, and 6 are amplifications. Further analyses revealed a core set of 12 regulatory processes or pathways that were each genetically altered in 70 % to 100 % of the samples. The data suggest that dysregulation of this core set of pathways is responsible for the major features of pancreatic tumorigenesis.