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公开(公告)号：US07704687B2
公开(公告)日：2010-04-27
申请号：US10705874
申请日：2003-11-13
CPC分类号： C12Q1/6841 , C12Q2565/102 , C12Q2537/157 , C12Q2521/313
摘要： Alterations in the genetic content of a cell underlie many human diseases, including cancers. A method called Digital Karyotyping provides quantitative analysis of DNA copy number at high resolution. This approach involves the isolation and enumeration of short sequence tags from specific genomic loci. Analysis of human cancer cells using this method identified gross chromosomal changes as well as amplifications and deletions, including regions not previously known to be altered. Foreign DNA sequences not present in the normal human genome could also be readily identified. Digital Karyotyping provides a broadly applicable means for systematic detection of DNA copy number changes on a genomic scale.
摘要翻译： 细胞遗传物质的变化是许多人类疾病，包括癌症的基础。 称为数字核型分析的方法提供高分辨率DNA拷贝数的定量分析。 这种方法涉及从特定基因组位点分离和枚举短序列标签。 使用该方法分析人类癌细胞鉴定出总体染色体变化以及扩增和缺失，包括以前未知已被改变的区域。 不存在于正常人类基因组中的外源DNA序列也可以容易地鉴定。 数字核型分析提供了广泛适用的方法，用于系统检测基因组规模上的DNA拷贝数变化。
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公开(公告)号：US20050202465A1
公开(公告)日：2005-09-15
申请号：US10996070
申请日：2004-11-24
申请人： Tian-Li Wang , Luis Diaz , Christoph Lengauer , Victor Velculescu , Kenneth Kinzler , Bert Vogelstein
发明人： Tian-Li Wang , Luis Diaz , Christoph Lengauer , Victor Velculescu , Kenneth Kinzler , Bert Vogelstein
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/136
摘要： Thymidylate synthase (TYMS) gene amplification was observed in 23% of 31 5-FU resistant liver metastases, while no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1021 days, p
摘要翻译： 在31例5-FU耐药性肝转移患者中，23例患者观察到胸苷酸合成酶（TYMS）基因扩增，而未用5-FU治疗的患者转移灶未观察到扩增。 含有TYMS扩增的转移患者的中位生存期（329天）比没有扩增的患者显着更短（1021天，p <0.01）。 TYMS的遗传扩增对复发性结肠直肠癌患者的治疗具有重要意义。
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3.发明申请公开(公告)号：US20130296408A1
公开(公告)日：2013-11-07
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
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
IPC分类号： C12Q1/68
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.
摘要翻译： 成神经管细胞瘤（MB）是儿童最常见的恶性脑肿瘤。 为了鉴定这种肿瘤类型的遗传改变，我们使用高密度微阵列搜索拷贝数变化，并使用Sanger测序对所有已知的蛋白质编码基因和miRNA基因进行测序。 我们发现平均每个肿瘤有11个基因改变，明显少于普通成年癌症。 除了Hedgehog和Wnt途径的改变之外，我们的分析导致了以前未知在MB中被改变的基因的发现。 最明显的是，在16％的MB患者中鉴定了组蛋白H3K4三甲基酶基因MLL2或MLL3的失活突变。 这些结果显示了成年和儿童期癌症遗传景观之间的关键差异，突出了发育途径的失调作为MBs的重要机制，并确定了特定类型的组蛋白甲基化在人类肿瘤发生中的作用。
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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.
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公开(公告)号：US20070031851A1
公开(公告)日：2007-02-08
申请号：US10915727
申请日：2004-08-11
IPC分类号： C12Q1/68 , C07H21/04 , C07K14/705
CPC分类号： C12Q1/6895 , C12Q1/6837 , C12Q2600/158
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 and other classes of drugs. They can be formed into arrays on solid supports for interrogation of a cell's transcriptome under various conditions.
摘要翻译： 描述在细胞周期期间差异表达的酵母基因。 它们可用于研究，影响和监测真核细胞的细胞周期。 它们可用于获得涉及细胞周期调节的人类同源物。 它们可用于鉴定抗真菌剂和其他类别的药物。 它们可以在固体支持物上形成阵列，用于在各种条件下询问细胞的转录组。
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公开(公告)号：US20090208505A1
公开(公告)日：2009-08-20
申请号：US10591347
申请日：2005-02-18
IPC分类号： A61K39/395 , C12Q1/68 , A61K31/7052 , C12Q1/48 , A61K31/5377 , A61K31/352 , C07H21/00 , A61P35/00
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： Phosphatidylinositol 3-kinases (PI3Ks) are known to be important regulators of signaling pathways. To determine whether PI3Ks are genetically altered in cancers, we analyzed the sequences of the P13K gene family and discovered that one family member, PIK3CA, is frequently mutated in cancers of the colon and other organs. The majority of mutations clustered near two positions within the P13K helical or kinase domains. PIK3CA represents one of the most highly mutated oncogenes yet identified in human cancers and is useful as a diagnostic and therapeutic target.
摘要翻译： 已知磷脂酰肌醇3-激酶（PI3K）是信号通路的重要调控因子。 为了确定PI3K在癌症中的遗传改变，我们分析了P13K基因家族的序列，发现一个家族成员PIK3CA在结肠癌和其他器官的癌症中经常发生突变。 大多数突变聚集在P13K螺旋或激酶结构域内的两个位置附近。 PIK3CA代表人类癌症中尚未鉴定的最高突变型癌基因之一，可用作诊断和治疗靶点。
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公开(公告)号：US20070037150A1
公开(公告)日：2007-02-15
申请号：US10544536
申请日：2004-02-18
CPC分类号： C12Q1/6886 , A61K31/506 , C12N9/1205 , C12Q1/025 , C12Q1/485 , C12Q1/6809 , C12Q1/6827 , C12Q2600/136 , C12Q2600/156 , G01N33/574
摘要： Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in −20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.
摘要翻译： 蛋白激酶是参与肿瘤发生的重要信号分子。 人类酪氨酸激酶基因家族（98个基因）的突变分析鉴定了-20％的结肠直肠癌的体细胞变化，大部分突变发生在NTRK3，FES，GUCY2F和以前称为MCCK / MLK4的未表征的酪氨酸激酶基因。 大多数改变是保守的残基影响激酶结构域的关键区域。 这些数据代表了癌症中信号转导基因的无偏见分析的范例，并为治疗干预提供了有用的目标。
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公开(公告)号：US07504493B2
公开(公告)日：2009-03-17
申请号：US10915727
申请日：2004-08-11
IPC分类号： C12N15/11
CPC分类号： C12Q1/6895 , C12Q1/6837 , C12Q2600/158
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 and other classes of drugs. They can be formed into arrays on solid supports for interrogation of a cell's transcriptome under various conditions.
摘要翻译： 描述在细胞周期期间差异表达的酵母基因。 它们可用于研究，影响和监测真核细胞的细胞周期。 它们可用于获得涉及细胞周期调节的人类同源物。 它们可用于鉴定抗真菌剂和其他类别的药物。 它们可以在固体支持物上形成阵列，用于在各种条件下询问细胞的转录组。
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公开(公告)号：US20050271586A1
公开(公告)日：2005-12-08
申请号：US11175478
申请日：2005-07-07
CPC分类号： C07F9/303 , A61K51/0489 , C07B59/004 , C07B2200/05
摘要： Aminophosphinic acid derivatives were synthesized as potential inhibitors of renal dipeptidase, an enzyme overexpressed in benign and malignant colon tumors. Several compounds showed potent enzyme-inhibitory activity. These compounds can be used therapeutically and diagnostically for treatment and detection of tumors.
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公开(公告)号：US06413727B1
公开(公告)日：2002-07-02
申请号：US08449731
申请日：1995-05-25
申请人： Hans Albertsen , Rakesh Anand , Mary Carlson , Joanna Groden , Philip John Hedge , Geoff Joslyn , Kenneth Kinzler , Alexander Fred Markham , Yusuke Nakamura , Andrew Thliveris , Bert Vogelstein , Raymond L. White
发明人： Hans Albertsen , Rakesh Anand , Mary Carlson , Joanna Groden , Philip John Hedge , Geoff Joslyn , Kenneth Kinzler , Alexander Fred Markham , Yusuke Nakamura , Andrew Thliveris , Bert Vogelstein , Raymond L. White
IPC分类号： G01N33574
CPC分类号： C07K14/47 , A01K2217/05 , C07K14/82 , C12Q1/68 , C12Q1/6827 , C12Q1/6886 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Q2600/172 , Y10S530/828
摘要： A human gene termed APC is disclosed. Methods and kits are provided for assessing mutations of the APC gene in human tissues and body samples. APC mutations are found in familial adenomatous polyposis patients as well as in sporadic colorectal cancer patients. APC is expressed in most normal tissues. These results suggest that APC is a tumor suppressor.
摘要翻译： 公开了一种称为APC的人类基因。 提供了用于评估人类组织和身体样品中APC基因突变的方法和试剂盒。 家族性腺瘤性息肉病患者以及散发性结肠直肠癌患者发现APC突变。 APC在大多数正常组织中表达。 这些结果表明APC是肿瘤抑制因子。
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