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. 发明申请

US20130210645A1 PERSONALIZED TUMOR BIOMARKERS 审中-公开
标题翻译：个性化肿瘤生物标志物
公开(公告)号：US20130210645A1
公开(公告)日：2013-08-15
申请号：US13579964
申请日：2011-02-17
申请人： Bert Volgelstein , Kenneth W. Kinzler , Victor Velculescu , Luis Diaz , Rebecca J. Leary
发明人： Bert Volgelstein , Kenneth W. Kinzler , Victor Velculescu , Luis Diaz , Rebecca J. Leary
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. We have developed a method, called personalized analysis of rearranged ends (PARE), which can identify translocations in solid tumors. Analysis of four colorectal and two breast cancers revealed an average of nine rearranged sequences (range 4 to 15) per tumor. Polymerase chain reaction with primers spanning the breakpoints were able to detect mutant DNA molecules present at levels lower than 0.001% and readily identified mutated circulating DNA in patient plasma samples. This approach provides an exquisitely sensitive and broadly applicable approach for the development of personalized biomarkers to enhance the clinical management of cancer patients.
摘要翻译：人类癌症的临床管理取决于对残留和复发性肿瘤的准确监测。我们开发了一种称为重排末端（PARE）的个性化分析方法，可以识别实体瘤易位。对4例结直肠癌和2例乳腺癌的分析显示，每个肿瘤平均有9个重排序列（范围4至15）。与跨越断点的引物的聚合酶链反应能够检测出低于0.001％的突变型DNA分子，并且容易鉴定出患者血浆样品中突变的循环DNA。这种方法为个性化生物标志物的开发提供了一种非常灵敏和广泛适用的方法，以加强癌症患者的临床管理。

2. 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。

3. 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。

4. 发明申请

US20120115735A1 Pathways Underlying Pancreatic Tumorigenesis and an Hereditary Pancreatic Cancer Gene 审中-公开
标题翻译：通路胰腺肿瘤发生和遗传性胰腺癌基因
公开(公告)号：US20120115735A1
公开(公告)日：2012-05-10
申请号：US13060453
申请日：2009-09-03
申请人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Sian Jones , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Scott Kern , Ralph Hruban , James R. Eshleman , Michael Goggins , Alison Klein
发明人： Bert Vogelstein , Kenneth W. Kinzler , D. Williams Parsons , Sian Jones , Xiaosong Zhang , Jimmy Cheng-Ho Lin , Rebecca J. Leary , Philipp Angenendt , Nickolas Papadopoulos , Victor Velculescu , Giovanni Parmigiani , Rachel Karchin , Scott Kern , Ralph Hruban , James R. Eshleman , Michael Goggins , Alison Klein
IPC分类号： C12Q1/68 , C40B20/00 , C07H21/04
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.
摘要翻译：目前对胰腺癌患者几乎没有治疗选择，迫切需要对这种致死性疾病的发病机理的新见解。为此，我们对24个胰腺肿瘤中改变的基因进行了综合分析。首先，我们从这些肿瘤的DNA中确定了23,781个转录本，代表20,583个蛋白质编码基因的序列。第二，我们使用微阵列查询每个样本中的百万个单核苷酸多态性的纯合缺失和扩增。第三，我们使用SAGE和下一代按序合成技术分析了相同样品的转录组。我们发现胰腺癌平均存在63个遗传改变，其中49个是点突变，8个是纯合缺失，6个是扩增。进一步的分析揭示了一组核心的12个调节过程或途径，在70％至100％的样品中进行了遗传改变。数据表明，这种核心途径的失调导致了胰腺肿瘤发生的主要特征。

5. 发明申请

US20140045881A1 GENES FREQUENTLY ALTERED IN PANCREATIC NEUROENDOCRINE TUMORS 审中-公开
标题翻译：普遍存在于胰腺神经元肿瘤中的基因
公开(公告)号：US20140045881A1
公开(公告)日：2014-02-13
申请号：US13977810
申请日：2012-01-04
申请人： Bert Vogelstein , Kenneth W. Kinzler , Victor Velculescu , Luis Diaz , Nikolas Papadopoulos , Yuchen Jiao , Ralph Hruban
发明人： Bert Vogelstein , Kenneth W. Kinzler , Victor Velculescu , Luis Diaz , Nikolas Papadopoulos , Yuchen Jiao , Ralph Hruban
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , G01N33/57438 , G01N2800/52
摘要： Pancreatic Neuroendocrine Tumors (PanNETs) are a rare but clinically important form of pancreatic neoplasia. To explore the genetic basis of PanNETs, we determined the exomic sequences of ten non-familial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. Remarkably, the most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN-1, which encodes menin, a component of a histone methyltransferase complex; and 43% had mutations in genes encoding either of the two subunits of a transcription/chromatin remodeling complex consisting of DAXX (death-domain associated protein) and ATRX (alpha thalassemia/mental retardation syndrome X-linked). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. We also found mutations in genes in the mTOR (mammalian target of rapamycin) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatment with mTOR inhibitors.
摘要翻译：胰腺神经内分泌肿瘤（Pannets）是一种罕见但临床上重要的胰腺肿瘤形式。为了探索PanNETs的遗传基础，我们确定了十个非家族PanNETs的外显子序列，然后筛选了58个额外的PanNET中最常见的突变基因。值得注意的是，最常突变的基因指定涉及染色质重塑的蛋白质：44％的肿瘤在MEN-1中具有体细胞失活突变，其编码menin，组蛋白甲基转移酶复合物的组分; 43％在编码由DAXX（死亡相关蛋白）和ATRX（α地中海贫血/智力迟钝综合征X连锁）组成的转录/染色质重塑复合物的两个亚基之一的基因中具有突变。在临床上，MEN1和DAXX / ATRX基因的突变与更好的预后相关。我们还发现在14％的肿瘤中mTOR（雷帕霉素的哺乳动物靶标）途径的基因突变，这种发现可能用于分层患者用mTOR抑制剂治疗。

6. 发明授权

US08709723B2 Integrated analyses of breast and colorectal cancers 有权
标题翻译：乳腺癌和结肠直肠癌的综合分析
公开(公告)号：US08709723B2
公开(公告)日：2014-04-29
申请号：US13461268
申请日：2012-05-01
申请人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
发明人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
IPC分类号： C12Q1/66 , C12P19/34 , C07H21/02
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes—deletion of all copies or amplification of at least twelve copies per cell—averaged thirteen per tumor. These data were integrated with previous mutation analysis of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analysis provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
摘要翻译：使用可以可靠地检测纯合缺失和扩增的方法对乳腺和结肠直肠肿瘤的拷贝数变化进行全基因组分析。通过主要拷贝数变化改变的基因数量 - 全部拷贝的缺失或每个细胞至少12个拷贝的扩增，平均每个肿瘤13个。这些数据与以前相同肿瘤类型的参考序列基因的突变分析结合起来，以鉴定受拷贝数变化和点变化影响的基因和细胞途径。富含遗传改变的途径包括控制细胞粘附，细胞内信号转导，DNA拓扑变化和细胞周期控制的途径。这些分析提供了在全基因组范围内的拷贝数和测序改变的综合视图，并确定了可用于癌症诊断和治疗的基因和途径。

7. 发明申请

US20100136560A1 Integrated Analyses of Breast and Colorectal Cancers 审中-公开
标题翻译：乳腺癌和结肠直肠癌综合分析
公开(公告)号：US20100136560A1
公开(公告)日：2010-06-03
申请号：US12619726
申请日：2009-11-17
申请人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
发明人： Bert Vogelstein , Kenneth W. Kinzler , Rebecca J. Leary , Victor E. Velculescu
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes—deletion of all copies or amplification of at least twelve copies per cell—averaged thirteen per tumor. These data were integrated with previous mutation analyses of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
摘要翻译：使用可以可靠地检测纯合缺失和扩增的方法对乳腺和结肠直肠肿瘤的拷贝数变化进行全基因组分析。通过主要拷贝数变化改变的基因数量 - 全部拷贝的缺失或每个细胞至少12个拷贝的扩增，平均每个肿瘤13个。这些数据与这些相同肿瘤类型中的参考序列基因的先前突变分析相结合，以鉴定受拷贝数变化和点改变影响的基因和细胞途径。富含遗传改变的途径包括控制细胞粘附，细胞内信号转导，DNA拓扑变化和细胞周期控制的途径。这些分析提供了在全基因组范围内的拷贝数和排序变化的综合视图，并确定了可用于癌症诊断和治疗的基因和途径。

8. 发明授权

US09637779B2 Antisense transcriptomes of cells 有权
公开(公告)号：US09637779B2
公开(公告)日：2017-05-02
申请号：US13131413
申请日：2009-12-02
申请人： Bert Vogelstein , Kenneth W. Kinzler , Yiping He , Victor Velculescu , Nickolas Papadopoulos
发明人： Bert Vogelstein , Kenneth W. Kinzler , Yiping He , Victor Velculescu , Nickolas Papadopoulos
IPC分类号： C12Q1/68 , G06F19/22
CPC分类号： C12Q1/6844 , G06F19/22 , C12Q2539/113 , C12Q2523/125 , C12Q2521/107
摘要： Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the Plus- or Minus-strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was non-random across the genome, and differed among cell types. Antisense transcripts thus appear to be a pervasive feature of human cells, suggesting that they are a fundamental component of gene regulation.

9. 发明授权

US09580750B2 P13K pathway mutations in cancer 有权
标题翻译：癌症中P13K通路突变
公开(公告)号：US09580750B2
公开(公告)日：2017-02-28
申请号：US11920860
申请日：2006-05-23
申请人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
发明人： Donald William Parsons , Tian-li Wang , Yardena Samuels , Alberto Bardelli , Christopher Lengauer , Victor Velculescu , Kenneth W. Kinzler , Bert Vogelstein
IPC分类号： C12Q1/62 , G01N33/574 , C07K16/40 , C12Q1/68 , C12Q1/48 , G01N33/50
CPC分类号： C12Q1/6883 , C12Q1/485 , C12Q2600/136 , C12Q2600/156 , G01N33/5044 , G01N33/57419
摘要： Given the important role of protein kinases in pathways affecting cellular growth and invasion, we have analyzed 340 serine/threonine kinases for genetic mutations in colorectal cancers. Mutations in eight genes were identified, including three members of the phosphatidylinositol-3-kinase (PI3K) pathway; the alterations in the latter genes each occurred in different tumors and did not overlap with mutations in PIK3CA or other non-serine-threonine kinase (STK) members of the PI3K pathway, suggesting that mutations in any of these genes had equivalent tumorigenic effects. These data demonstrate that the PI3K pathway is a major target for mutational activation in colorectal cancers and provide new opportunities for therapeutic intervention.
摘要翻译：鉴于蛋白激酶在影响细胞生长和侵袭的途径中的重要作用，我们已经分析了340个丝氨酸/苏氨酸激酶在结肠直肠癌中的遗传突变。鉴定出8个基因的突变，包括磷脂酰肌醇-3-激酶（PI3K）通路的3个成员; 后一种基因的改变各自发生在不同的肿瘤中，并且不与PIK3CA或PI3K途径的其他非丝氨酸 - 苏氨酸激酶（STK）成员的突变重叠，这表明任何这些基因中的突变具有相等的致瘤作用。这些数据表明，PI3K途径是结肠直肠癌突变激活的主要靶标，为治疗干预提供新的机会。

10. 发明申请

US20120009573A1 Antisense Transcriptomes of Cells 有权
标题翻译：细胞反义转录组
公开(公告)号：US20120009573A1
公开(公告)日：2012-01-12
申请号：US13131413
申请日：2009-12-02
申请人： Bert Vogelstein , Kenneth W. Kinzler , Yiping He , Victor Velculescu , Nickolas Papadopoulos
发明人： Bert Vogelstein , Kenneth W. Kinzler , Yiping He , Victor Velculescu , Nickolas Papadopoulos
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6844 , G06F19/22 , C12Q2539/113 , C12Q2523/125 , C12Q2521/107
摘要： Transcription in mammalian cells can be assessed at a genome-wide level, but it has been difficult to reliably determine whether individual transcripts are derived from the Plus- or Minus-strands of chromosomes. This distinction can be critical for understanding the relationship between known transcripts (sense) and the complementary antisense transcripts that may regulate them. Here we describe a technique that can be used to (i) identify the DNA strand of origin for any particular RNA transcript and (ii) quantify the number of sense and antisense transcripts from expressed genes at a global level. We examined five different human cell types and in each case found evidence for antisense transcripts in 2900 to 6400 human genes. The distribution of antisense transcripts was distinct from that of sense transcripts, was non-random across the genome, and differed among cell types. Anti-sense transcripts thus appear to be a pervasive feature of human cells, suggesting that they are a fundamental component of gene regulation.
摘要翻译：哺乳动物细胞中的转录可以在全基因组范围内进行评估，但是难以可靠地确定个体转录本是否衍生自染色体的加号或阴影链。这种区别对于了解已知转录物（有义）和可能调节它们的互补反义转录物之间的关系可能是至关重要的。在这里，我们描述了一种可用于（i）识别任何特定RNA转录物的DNA链起源的技术，（ii）在全球范围内量化来自表达基因的正义和反义转录本的数量。我们检查了五种不同的人类细胞类型，并且在每种情况下都发现2900至6400个人类基因中的反义转录物的证据。反义转录物的分布与有义转录物的分布不同，在基因组中是非随机的，并且在细胞类型之间不同。因此，反义转录物似乎是人类细胞的普遍特征，表明它们是基因调控的基本组成部分。

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