专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明授权

US09873917B2 Oligodendroglioma drive genes 有权
公开(公告)号：US09873917B2
公开(公告)日：2018-01-23
申请号：US14233296
申请日：2012-07-18
申请人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger McLendon
发明人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger McLendon
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158
摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.

2. 发明申请

US20140221219A1 OLIGODENDROGLIOMA DRIVE GENES 审中-公开
标题翻译： OLIGODENDROGLIOMA驱动基因
公开(公告)号：US20140221219A1
公开(公告)日：2014-08-07
申请号：US14233296
申请日：2012-07-18
申请人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger Mclendon
发明人： Bert Vogelstein , Kenneth W. Kinzler , Chetan Bettegowda , Nishant Agrawal , Nickolas Papadopoulos , Darell Bigner , Hai Yan , Roger Mclendon
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158
摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.
摘要翻译：少突神经胶质瘤是成人中第二常见的恶性脑肿瘤。这些肿瘤通常包含染色体异常，涉及染色体1和染色体1的致晕体融合，导致前者的整个短臂和后者的长臂的损失。为了确定这种改变的分子遗传基础，我们对染色体1p和19q损失进行了7个分离性少突胶质细胞瘤的外切测序。在其他变化中，我们发现在七种病例中的六种中，染色体19q上的CIC（果蝇基因capicua的同系物）被体细胞突变，并且染色体1p上的FUBP1（远上游元件（FUSE）结合蛋白）在两个体内被突变的七例。另外27例少突胶质细胞瘤的检查显示有12例和3例分别具有CIC和FUBP1突变的肿瘤，其中58％预计会导致编码蛋白的截短。这些结果表明这些基因在少突胶质细胞的生物学和病理学中的关键作用。

3. 发明授权

US08685660B2 Genetic alterations in isocitrate dehydrogenase and other genes in malignant glioma 有权
标题翻译：异柠檬酸脱氢酶和恶性胶质瘤中其他基因的遗传改变
公开(公告)号：US08685660B2
公开(公告)日：2014-04-01
申请号：US13060191
申请日：2009-09-03
申请人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan , Gregory J. Riggins
发明人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan , Gregory J. Riggins
IPC分类号： G01N33/574
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：我们发现大多数II级和III级星形细胞瘤和少突胶质细胞瘤中异柠檬酸脱氢酶1（IDH1）的R132残基突变以及从这些较低级别病变发展的成胶质细胞瘤。那些没有IDH1突变的肿瘤在紧密相关的IDH2基因的类似R172残基中经常具有突变。这些发现对恶性胶质瘤的发病机制和诊断具有重要意义。

4. 发明授权

US09982306B2 Somatic mutations in ATRX in brain cancer 有权
公开(公告)号：US09982306B2
公开(公告)日：2018-05-29
申请号：US14129850
申请日：2012-06-28
申请人： Hai Yan , Darell Bigner , Bert Vogelstein , Kenneth W. Kinzler , Alan Meeker , Ralph Hruban , Nickolas Papadopoulos , Luis Diaz , Yuchen Jiao
发明人： Hai Yan , Darell Bigner , Bert Vogelstein , Kenneth W. Kinzler , Alan Meeker , Ralph Hruban , Nickolas Papadopoulos , Luis Diaz , Yuchen Jiao
IPC分类号： G01N33/68 , C12Q1/68 , G01N33/574 , C07K16/40 , C12N15/113
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.

5. 发明申请

US20140227271A1 SOMATIC MUTATIONS IN ATRX IN BRAIN CANCER 有权
标题翻译：脑癌中ATRX中的SOMATIC MUTATIONS
公开(公告)号：US20140227271A1
公开(公告)日：2014-08-14
申请号：US14129850
申请日：2012-06-28
申请人： Hai Yan , Darell Bigner , Bert Vogelstein , Kenneth W. Kinzler , Alan Meeker , Ralph Hruban , Nickolas Papadopoulos , Luis Diaz , Yuchen Jiao
发明人： Hai Yan , Darell Bigner , Bert Vogelstein , Kenneth W. Kinzler , Alan Meeker , Ralph Hruban , Nickolas Papadopoulos , Luis Diaz , Yuchen Jiao
IPC分类号： C12Q1/68 , C07K16/40 , C12N15/113 , G01N33/574
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：我们确定了来自各个位点的447例癌症中ATRX和DAXX的序列。我们发现多形性小儿多形性成胶质细胞瘤（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％）中最常见的突变; 并且表明，在未激活端粒酶的癌症中发现端粒酶不依赖端粒维持机制的替代延长端粒（ALT）与任一基因的体细胞突变完全相关。相比之下，成骨细胞瘤和卵巢，乳腺和胰腺腺癌对于ATRX和DAXX中的突变是阴性的。 ATRX或DAXX中的改变定义了与人类癌症中替代端粒维持功能密切相关的特定分子途径。

6. 发明申请

US20110229479A1 GENETIC ALTERATIONS IN ISOCITRATE DEHYDROGENASE AND OTHER GENES IN MALIGNANT GLIOMA 有权
标题翻译：异烟肼脱氢酶和其他基因在恶性胶质瘤中的遗传变异
公开(公告)号：US20110229479A1
公开(公告)日：2011-09-22
申请号：US13060191
申请日：2009-09-03
申请人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan
发明人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Sian Jones , Hai Yan , Darell Bigner , Chien-Tsun Kuan
IPC分类号： A61K39/395 , C12Q1/68 , G01N33/574 , C07K16/32 , A61K39/00 , C12N9/04 , C07H21/04 , C12Q1/32 , A61P37/04 , A61P35/00
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：我们发现大多数II级和III级星形细胞瘤和少突胶质细胞瘤中异柠檬酸脱氢酶1（IDH1）的R132残基突变以及从这些较低级别病变发展的成胶质细胞瘤。那些没有IDH1突变的肿瘤在紧密相关的IDH2基因的类似R172残基中经常具有突变。这些发现对恶性胶质瘤的发病机制和诊断具有重要意义。

7. 发明授权

US09695479B2 Medulloblastoma genes as targets for diagnosis and therapeutics 有权
公开(公告)号：US09695479B2
公开(公告)日：2017-07-04
申请号：US13884154
申请日：2011-11-08
申请人： Bert Vogelstein , Kenneth Kinzler , Nickolas Papadopoulos , Donald Williams Parsons , Rebecca J. Leary , Meng Li , Xiaosong Zhang , Sian Jones , Gregory J. Riggins , Victor Velculescu , Darell Bigner , Hai Yan
发明人： Bert Vogelstein , Kenneth Kinzler , Nickolas Papadopoulos , Donald Williams Parsons , Rebecca J. Leary , Meng Li , Xiaosong Zhang , Sian Jones , Gregory J. Riggins , Victor Velculescu , Darell Bigner , Hai Yan
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156 , G01N33/57407
摘要： Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone H3K4 trimethylase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.

8. 发明授权

US07045352B2 Converting diploidy to haploidy for genetic diagnosis 失效
公开(公告)号：US07045352B2
公开(公告)日：2006-05-16
申请号：US10210066
申请日：2002-08-02
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
IPC分类号： C12N5/12 , C12Q1/00 , C12N15/06 , C12N15/87
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.

9. 发明授权

US06475794B1 Converting diploidy to haploidy for genetic diagnosis 有权
标题翻译：将二倍体转化为单倍体用于遗传诊断
公开(公告)号：US06475794B1
公开(公告)日：2002-11-05
申请号：US09504860
申请日：2000-02-16
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Hai Yan
IPC分类号： C12N1502
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.
摘要翻译：与遗传性疾病相关的突变的检测由于哺乳动物细胞的二倍体性质而复杂化。存在于一个等位基因中的突变通常被其他等位基因的野生型序列掩蔽。可以从单次融合产生的体细胞杂交体内的每个染色体分离个体等位基因。来自杂种的核酸可以以明确的方式分析突变。这种方法被用于检测先前不符合遗传诊断的两种致癌突变。研究的家庭之一，Warthin Family G，是生物医学文献中描述的第一个遗传性结肠癌综合症患者。

10. 发明授权

US09476095B2 Safe sequencing system 有权
标题翻译：安全排序系统
公开(公告)号：US09476095B2
公开(公告)日：2016-10-25
申请号：US14111715
申请日：2012-04-12
申请人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Isaac Kinde
发明人： Bert Vogelstein , Kenneth W. Kinzler , Nickolas Papadopoulos , Isaac Kinde
IPC分类号： C12Q1/68 , C07H21/02
CPC分类号： C12Q1/6874 , C12Q1/6806 , C12Q1/6869 , C12Q1/6876 , C12Q2563/179 , C12Q2600/158 , C12Q2535/122 , C12Q2565/514
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.
摘要翻译：存在于DNA模板的一小部分中的突变的鉴定对于在几个生物医学研究领域的进展是必不可少的。尽管大规模并行测序仪器原则上非常适合于此任务，但是这些仪器中的错误率通常太高，无法确定罕见的变体。我们在这里描述了一种可以显着增加大规模并行测序仪器对此目的的灵敏度的方法。这种方法的一个例子是（Safe-Sequencing System），称为“Safe-SeqS”，包括（i）将唯一标识符（UID）分配给每个模板分子; （ii）每个唯一标记的模板分子的扩增以产生UID家族; 和（iii）扩增产物的冗余测序。具有相同UID的PCR片段是真实的突变体（“超突变体”），如果其≥95％含有相同的突变。我们说明了这种方法用于确定聚合酶的保真度，体外合成的寡核苷酸的准确性以及正常细胞的核和线粒体基因组中突变的流行率的效用。

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式