公开(公告)号：US10144971B2

公开(公告)日：2018-12-04

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 ,  C12P19/34 ,  C12Q1/6886 ,  G01N33/574

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.

公开(公告)号：US06511799B1

公开(公告)日：2003-01-28

申请号：US09311551

申请日：1999-05-14

申请人： Luis daCosta ,  Bert Vogelstein ,  Kenneth W Kinzler ,  Tong-Chuan He

发明人： Luis daCosta ,  Bert Vogelstein ,  Kenneth W Kinzler ,  Tong-Chuan He

IPC分类号： C12Q100

CPC分类号： C07K14/4702 ,  C07K14/705 ,  C12Q1/6897

摘要： Human CDX2, a homeobox gene, has been identified as a downstream effector of tumor suppressor APC. APC induces the transcription of CDX2. This newly found relationship permits specific drug screening assays as well as therapeutic and diagnostic methods.

摘要翻译： 人CDX2是同源盒基因，已被鉴定为肿瘤抑制因子APC的下游效应物。 APC诱导CDX2的转录。 这种新发现的关系允许特定的药物筛选测定以及治疗和诊断方法。

公开(公告)号：US08048627B2

公开(公告)日：2011-11-01

申请号：US10562840

申请日：2004-06-09

申请人： Devin Dressman ,  Hai Yan ,  Kenneth W Kinzler ,  Bert Vogelstein

发明人： Devin Dressman ,  Hai Yan ,  Kenneth W Kinzler ,  Bert Vogelstein

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/02

CPC分类号： C12Q1/6858 ,  C07H21/04 ,  C12N15/1075 ,  C12Q1/686 ,  C12Q2565/537 ,  C12Q2563/149 ,  C12Q2563/143

摘要： Many areas of biomedical research depend on the analysis of uncommon variations in individual genes or transcripts. Here we describe a method that can quantify such variation at a scale and ease heretofore unattainable. Each DNA molecule in a collection of such molecules is converted into a single particle to which thousands of copies of DNA identical in sequence to the original are bound. This population of beads then corresponds to a one-to-one representation of the starting DNA molecules. Variation within the original population of DNA molecules can then be simply assessed by counting fluorescently-labeled particles via flow cytometry. Millions of individual DNA molecules can be assessed in this fashion with standard laboratory equipment. Moreover, specific variants can be isolated by flow sorting and employed for further experimentation. This approach can be used for the identification and quantification of rare mutations as well as to study variations in gene sequences or transcripts in specific populations or tissues.

摘要翻译： 生物医学研究的许多领域取决于对个别基因或转录本中不常见变异的分析。 在这里，我们描述一种可以量化这种变化的方法，其规模和容易度迄今为止是无法实现的。 将这样的分子的集合中的每个DNA分子转化成单个颗粒，其中与原始序列顺序相同的数千个拷贝的DNA被结合。 这种珠子群对应于起始DNA分子的一对一表示。 然后可以通过流式细胞术对荧光标记的颗粒进行计数，简单地评估原始DNA分子群体内的变异。 可以用标准实验室设备以这种方式评估数百万个单独的DNA分子。 此外，可以通过流动分选分离特定的变体并用于进一步的实验。 该方法可用于鉴定和定量稀有突变，并研究特定群体或组织中基因序列或转录本的变异。

公开(公告)号：US09360526B2

公开(公告)日：2016-06-07

申请号：US12091395

申请日：2006-10-20

申请人： Bert Vogelstein ,  Frank Diehl ,  Kenneth W Kinzler ,  Meng Li

发明人： Bert Vogelstein ,  Frank Diehl ,  Kenneth W Kinzler ,  Meng Li

IPC分类号： C12Q1/68 ,  C12P19/34 ,  G01R31/327 ,  G01R31/02

CPC分类号： C12Q1/6858 ,  G01R31/025 ,  G01R31/3277 ,  C12Q2565/537 ,  C12Q2563/155 ,  C12Q2527/125

摘要： Improvements on the basic method used for BEAMing increase sensitivity and increase the signal-to-noise ratio. The improvements have permitted the determination of intrinsic error rates of various DNA polymerases and have permitted the detection of rare and subtle mutations in DNA isolated from plasma of cancer patients.

摘要翻译： 用于BEAMing的基本方法的改进提高了灵敏度并提高了信噪比。 这些改进允许确定各种DNA聚合酶的固有错误率，并允许检测从癌症患者血浆中分离的DNA中罕见且微妙的突变。

公开(公告)号：US09328343B2

公开(公告)日：2016-05-03

申请号：US13311120

申请日：2011-12-05

申请人： Devin Dressman ,  Hai Yan ,  Kenneth W Kinzler ,  Bert Vogelstein

发明人： Devin Dressman ,  Hai Yan ,  Kenneth W Kinzler ,  Bert Vogelstein

IPC分类号： C12Q1/68 ,  C12N15/10 ,  C07H21/04

CPC分类号： C12Q1/6858 ,  C07H21/04 ,  C12N15/1075 ,  C12Q1/686 ,  C12Q2565/537 ,  C12Q2563/149 ,  C12Q2563/143

摘要： Many areas of biomedical research depend on the analysis of uncommon variations in individual genes or transcripts. Here we describe a method that can quantify such variation at a scale and ease heretofore unattainable. Each DNA molecule in a collection of such molecules is converted into a single particle to which thousands of copies of DNA identical in sequence to the original are bound. This population of beads then corresponds to a one-to-one representation of the starting DNA molecules. Variation within the original population of DNA molecules can then be simply assessed by counting fluorescently-labeled particles via flow cytometry. Millions of individual DNA molecules can be assessed in this fashion with standard laboratory equipment. Moreover, specific variants can be isolated by flow sorting and employed for further experimentation. This approach can be used for the identification and quantification of rare mutations as well as to study variations in gene sequences or transcripts in specific populations or tissues.

摘要翻译： 生物医学研究的许多领域取决于对个别基因或转录本中不常见变异的分析。 在这里，我们描述一种可以量化这种变化的方法，其规模和容易度迄今为止是无法实现的。 将这样的分子的集合中的每个DNA分子转化成单个颗粒，其中与原始序列顺序相同的数千个拷贝的DNA被结合。 这种珠子群对应于起始DNA分子的一对一表示。 然后可以通过流式细胞术对荧光标记的颗粒进行计数，简单地评估原始DNA分子群体内的变异。 可以用标准实验室设备以这种方式评估数百万个单独的DNA分子。 此外，可以通过流动分选分离特定的变体并用于进一步的实验。 该方法可用于鉴定和定量稀有突变，并研究特定群体或组织中基因序列或转录本的变异。