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    SOMATIC MUTATIONS IN ATRX IN BRAIN CANCER
    6.
    发明申请
    SOMATIC MUTATIONS IN ATRX IN BRAIN CANCER 有权
    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。

    MUTATIONS IN PANCREATIC NEOPLASMS
    8.
    发明申请
    MUTATIONS IN PANCREATIC NEOPLASMS 有权
    。。。。。。。。。

    公开(公告)号：US20140179538A1

    公开(公告)日：2014-06-26

    申请号：US14128478

    申请日：2012-06-22

    申请人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Jian Wu ,  Luis Diaz ,  Nickolas Papadopoulos ,  Hanno Matthaei ,  Ralph Hruban ,  Anirban Maitra

    发明人： Bert Vogelstein ,  Kenneth W. Kinzler ,  Jian Wu ,  Luis Diaz ,  Nickolas Papadopoulos ,  Hanno Matthaei ,  Ralph Hruban ,  Anirban Maitra

    IPC分类号： C12Q1/68

    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。 我们发现GNAS密码子201的复发性突变。 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，我们可以调查与含有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突变可以通过诊断和管理囊性胰腺病变患者。

    GENES FREQUENTLY ALTERED IN PANCREATIC NEUROENDOCRINE TUMORS
    10.
    发明申请
    GENES FREQUENTLY ALTERED IN PANCREATIC NEUROENDOCRINE TUMORS 审中-公开
    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。