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

WO2010028098A3 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 审中-公开
标题翻译：基于胰腺癌和胰腺癌基因的途径
公开(公告)号：WO2010028098A3
公开(公告)日：2010-06-10
申请号：PCT/US2009055802
申请日：2009-09-03
申请人： UNIV JOHNS HOPKINS , 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
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： This invention relates to new insights into the pathogenesis of pancreatic cancers by analyzing 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：本发明涉及通过分析24个胰腺肿瘤中改变的基因对胰腺癌发病机理的新见解。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。其次，我们使用微阵列查询了每个样本中一百万个单核苷酸多态性的纯合缺失和扩增。第三，我们使用SAGE和下一代合成技术分析相同样品的转录组我们发现胰腺癌平均含有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。

2. 发明申请

WO2010028098A4 PATHWAYS UNDERLYING PANCREATIC TUMORIGENESIS AND AN HEREDITARY PANCREATIC CANCER GENE 审中-公开
标题翻译：胰岛素瘤和遗传性胰腺癌基因途径
公开(公告)号：WO2010028098A4
公开(公告)日：2010-08-19
申请号：PCT/US2009055802
申请日：2009-09-03
申请人： UNIV JOHNS HOPKINS , 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
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： This invention relates to new insights into the pathogenesis of pancreatic cancers by analyzing 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：本发明涉及通过分析在24个胰腺肿瘤中改变的基因而对胰腺癌的发病机理的新见解。首先，我们确定了来自这些肿瘤的DNA中23,781个转录物的序列，代表20,583个蛋白质编码基因。其次，我们使用微阵列查询每个样本中一百万个单核苷酸多态性来寻找纯合子缺失和扩增。第三，我们使用SAGE和下一代合成测序技术分析了相同样品的转录组我们发现胰腺癌平均含有63个基因改变，其中49个是点突变，8个是纯合子缺失，6个是扩增。进一步的分析揭示了12个监管程序或途径的核心组合，每个过程或途径在70％到100％的样本中均被遗传改变。数据表明这种核心途径的失调调节是胰腺肿瘤发生的主要特征的原因。

3. 发明申请

WO2010102160A3 DIAGNOSTIC METHOD USING PALB2 审中-公开
标题翻译：诊断方法使用PALB2
公开(公告)号：WO2010102160A3
公开(公告)日：2011-01-13
申请号：PCT/US2010026290
申请日：2010-03-05
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON , HIDALGO MANUEL , VELCULESCU VICTOR E
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PARSONS D WILLIAMS , JONES SIAN , KERN SCOTT , HRUBAN RALPH , ESHLEMAN JAMES R , GOGGINS MICHAEL , KLEIN ALISON , HIDALGO MANUEL , VELCULESCU VICTOR E
IPC分类号： C12Q1/68 , G01N33/574 , G01N33/68
CPC分类号： C12Q1/6886 , A61K31/407 , C12Q2600/106 , C12Q2600/156 , C12Q2600/158 , G01N33/57438 , G01N2333/47
摘要： The present invention provides a method for detecting mutations in the PALB2 gene in pancreatic cancer patients and in individuals having a family history of pancreatic cancer. Methods are also provided for diagnosing a predisposition to pancreatic cancer, for predicting a patient's response to pancreatic cancer therapies, and for treating pancreatic cancer, based on presence of a PALB2 mutation or abberant PALB2 gene expression in a patient.
摘要翻译：本发明提供了一种检测胰腺癌患者和具有胰腺癌家族史的个体中PALB2基因突变的方法。还提供了用于诊断患有胰腺癌的倾向，用于预测患者对胰腺癌治疗的反应以及用于治疗患者胰腺癌的方法，其基于在患者体内PALB2突变或异常PALB2基因表达的存在。

4. 发明申请

WO2012064721A2 MEDULLOBLASTOMA GENES AS TARGETS FOR DIAGNOSIS AND THERAPEUTICS 审中-公开
标题翻译：作为诊断和治疗目标的MEDLOBLASTOMA基因
公开(公告)号：WO2012064721A2
公开(公告)日：2012-05-18
申请号：PCT/US2011059751
申请日：2011-11-08
申请人： UNIV JOHNS HOPKINS , UNIV DUKE , VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , PARSONS DONALD WILLIAMS , LEARY REBECCA J , LI MENG , ZHANG XIAOSONG , JONES SIAN , RIGGINS GREGORY J , VELCULESCU VICTOR , BIGNER DARELL , YAN HAI
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , PARSONS DONALD WILLIAMS , LEARY REBECCA J , LI MENG , ZHANG XIAOSONG , JONES SIAN , RIGGINS GREGORY J , VELCULESCU VICTOR , BIGNER DARELL , YAN HAI
IPC分类号： G01N33/574 , C12Q1/68 , G01N33/50
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：髓母细胞瘤（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改变，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。我们发现平均而言，每个肿瘤有11个基因改变，明显少于常见的成人癌症。除了Hedgehog和Wnt途径的改变之外，我们的分析还导致发现以前不知道在MB中改变的基因。最值得注意的是，在16％的MB患者中鉴定出组蛋白H3K4三甲基化酶基因MLL2或MLL3的失活突变。这些结果表明成人和儿童癌症的遗传景观之间的主要区别，突出发展途径的失调作为潜在的MB的重要机制，并确定在人类肿瘤特定类型的组蛋白甲基化的作用。

5. 发明申请

WO2009049166A2 GENOMIC LANDSCAPES OF HUMAN BREAST AND COLORECTAL CANCERS 审中-公开
标题翻译：人类乳腺癌和色素沉着病的基因组学观察
公开(公告)号：WO2009049166A2
公开(公告)日：2009-04-16
申请号：PCT/US2008079526
申请日：2008-10-10
申请人： UNIV JOHNS HOPKINS , WOOD LAURA D , PARSONS D WILLIAMS , JONES SIAN , LIN JIMMY , SJOEBLOM TOBIAS , BARBER THOMAS , PARMIGIANI GIOVANNI , VELCULESCU VICTOR , KINZLER KENNETH W , VOGELSTEIN BERT
发明人： WOOD LAURA D , PARSONS D WILLIAMS , JONES SIAN , LIN JIMMY , SJOEBLOM TOBIAS , BARBER THOMAS , PARMIGIANI GIOVANNI , VELCULESCU VICTOR , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： C12Q1/68 , C12Q1/02
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156
摘要： Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalogue the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
摘要翻译：人类癌症是由致癌基因和肿瘤抑制基因突变的积累引起的。为了列出肿瘤发生过程中发生的遗传变化，我们从11个乳腺和11个结肠直肠肿瘤中分离出DNA，并在这些样品中确定了参考序列数据库中的基因序列。根据对18,191个基因的20,857个转录本的外显子的分析，我们得出结论，乳腺癌和结肠直肠癌的基因组景观由少数常见的突变基因“山”组成，更多的基因“山”在低位突变频率。我们描述了统计和生物信息学工具，可以帮助识别在肿瘤发生中发挥作用的突变。这些结果有助于了解人类癌症的性质和异质性以及使用个人基因组学进行肿瘤诊断和治疗。

6. 发明申请

WO2012071096A3 ARID1A AND PPP2R1A MUTATIONS IN CANCER 审中-公开
标题翻译：癌症中的ARID1A和PPP2R1A突变
公开(公告)号：WO2012071096A3
公开(公告)日：2012-08-16
申请号：PCT/US2011050487
申请日：2011-09-06
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , PAPADOPOULOS NICKOLAS , JONES SIAN
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , PAPADOPOULOS NICKOLAS , JONES SIAN
IPC分类号： C12Q1/68 , A61K31/7088 , C12N5/09 , C12N15/11 , G01N33/68
CPC分类号： C12Q1/6886 , A61K31/7088 , A61K31/711 , C12Q2600/156 , G01N33/5011
摘要： Two genes, ARID1A (AT-rich interactive domain-containing protein 1A) and PPP2R1A (protein-phosphatase 2, regulatory subunit 1, alpha), can be used in methods which are useful for detecting cancer, diagnosing cancer, contributing to a diagnosis of cancer, confirming a diagnosis of cancer, identifying appropriate treatments for cancer, monitoring treatment of cancer, and evaluating treatment protocols for cancer, including ovarian clear cell carcinoma, breast cancer, colon cancer, gastric cancer, lung cancer, medulloblastoma, pancreatic cancer, and prostate cancer.
摘要翻译：可用于检测癌症，诊断癌症，有助于诊断癌症的方法中使用两种基因ARID1A（含AT富含交互结构域的蛋白质1A）和PPP2R1A（蛋白质磷酸酶2，调节亚单位1，α）确定癌症的诊断，确定癌症的适当治疗，监测癌症的治疗，以及评估癌症的治疗方案，包括卵巢透明细胞癌，乳腺癌，结肠癌，胃癌，肺癌，成神经管细胞瘤，胰腺癌和前列腺癌。

7. 发明申请

WO2011103236A3 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：WO2011103236A3
公开(公告)日：2012-02-09
申请号：PCT/US2011025152
申请日：2011-02-17
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , DIAZ LUIS , LEARY REBECCA J
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , DIAZ LUIS , LEARY REBECCA J
IPC分类号： C12Q1/68 , C12N15/11 , C40B40/06
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。

8. 发明申请

WO2012178034A2 MUTATIONS IN PANCREATIC NEOPLASMS 审中-公开
标题翻译：胰腺神经细胞的突变
公开(公告)号：WO2012178034A2
公开(公告)日：2012-12-27
申请号：PCT/US2012043783
申请日：2012-06-22
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , WU JIAN , DIAZ LUIS , PAPADOPOULOS NICKOLAS , MATTHAEI HANNO , HRUBAN RALPH , MAITRA ANIRBAN
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , WU JIAN , DIAZ LUIS , PAPADOPOULOS NICKOLAS , MATTHAEI HANNO , HRUBAN RALPH , MAITRA ANIRBAN
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156
摘要： To help reveal the pathogenesis of these lesions, we purified the DNA from Intraductal Papillary Mucinous Neoplasm (IPMN) cyst fluids from 19 patients and searched for mutations in 169 genes commonly altered in human cancers. We identified recurrent mutations at codon 201 of GNAS. We found that GNAS mutations were present in 66% of IPMNs and that either KRAS or GNAS mutations could be identified in 96%. In eight cases, we could investigate invasive adenocarcinomas that developed in association with IPMNs containing GNAS mutations. In seven of these eight cases, the GNAS mutations present in the IPMNs were also found in the invasive lesion. GNAS mutations were not found in other types of cystic neoplasms of the pancreas or in invasive adenocarcinomas not associated with IPMNs. These data suggest that GNAS mutations can inform the diagnosis and management of patients with cystic pancreatic lesions.
摘要翻译：为了揭示这些病变的发病机制，我们从19名患者的导管内乳头状粘液性肿瘤（IPMN）囊肿液中纯化DNA，并搜索了在人类癌症中通常改变的169种基因中的突变。我们在GNAS的201号密码子处鉴定了复发性突变。我们发现GNAS突变存在于66％的IPMNs中，KRAS或GNAS突变可以在96％中鉴定。在8例中，我们可以研究与含有GNAS突变的IPMN相关的侵袭性腺癌。在这8例中有7例中，存在于IPMNs中的GNAS突变也在侵袭性损伤中发现。在其他类型的胰腺囊性肿瘤或与IPMN无关的侵袭性腺癌中未发现GNAS突变。这些数据表明，GNAS突变可以为囊性胰腺病变患者的诊断和治疗提供依据。

9. 发明申请

WO2010065576A2 THE ANTISENSE TRANSCRIPTOMES OF CELLS 审中-公开
标题翻译：细胞的抗原转录物
公开(公告)号：WO2010065576A2
公开(公告)日：2010-06-10
申请号：PCT/US2009066313
申请日：2009-12-02
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , HE YIPING , VELCULESCU VICTOR , PAPADOPOULOS NICKOLAS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , HE YIPING , VELCULESCU VICTOR , PAPADOPOULOS NICKOLAS
IPC分类号： C12N15/11 , 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.
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。

10. 发明申请

WO2012094401A3 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：WO2012094401A3
公开(公告)日：2012-10-18
申请号：PCT/US2012020199
申请日：2012-01-04
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , DIAZ LUIS , PAPADOPOULOS NIKOLAS , JIAO YUCHEN , HRUBAN RALPH
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , VELCULESCU VICTOR , DIAZ LUIS , PAPADOPOULOS NIKOLAS , JIAO YUCHEN , HRUBAN RALPH
IPC分类号： C12Q1/68 , G01N33/574 , G01N33/58
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。

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