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1. 发明申请

WO2008100913A3 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：早期检测和预防结肠癌
公开(公告)号：WO2008100913A3
公开(公告)日：2008-12-18
申请号：PCT/US2008053689
申请日：2008-02-12
申请人： UNIV JOHNS HOPKINS , ONCOMETHYLOME SCIENCES SA , BAYLIN STEPHEN B , SCHUEBEL KORNEL E , CRIEKINGE WIM VAN
发明人： BAYLIN STEPHEN B , SCHUEBEL KORNEL E , CRIEKINGE WIM VAN
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2523/125 , C12Q2600/106 , C12Q2600/154
摘要： We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island hypermethylation and transcriptional silencing in colorectal cancer (CRC). By screening cell lines and validating tumor specific hypermethylation in a panel of primary human CRC samples, we estimate that nearly 5% of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find a much larger number of genes hypermethylated in individual tumors, and much higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken. The genes we identified can be used inter alia diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：我们已经开发了一种转录组范围的方法来鉴定受启动子CpG岛高甲基化和转录沉默在结肠直肠癌（CRC）中影响的基因。通过筛选细胞系并验证一组原代人CRC样品中的肿瘤特异性高甲基化，我们估计所有已知基因中的近5％可能是单个肿瘤中的启动子甲基化。当与基因突变直接比较时，我们发现在个体肿瘤中超甲基化的基因数量更多，并且在具有遗传或表观遗传变化的个体基因内的高甲基化频率高得多。因此，为了列举人类癌症基因组中的全部变化，并促进最有效的肿瘤分组以鉴定癌症生物标志物并定制治疗方法，应进行遗传和表观遗传筛选。我们确定的基因可以用于诊断上检测癌症，癌前病症和发展癌症的可能性。

2. 发明申请

WO2008010975A3 EARLY DETECTION AND PROGNOSIS OF COLON CANCERS 审中-公开
标题翻译：早期检测和预防结肠癌
公开(公告)号：WO2008010975A3
公开(公告)日：2008-12-31
申请号：PCT/US2007016104
申请日：2007-07-16
申请人： UNIV JOHNS HOPKINS , ONCOMETHYLOME SCIENCES S A , BAYLIN STEPHEN B , CRIEKINGE WIM VAN , SCHUEBEL KORNEL E , COPE LESLIE , SUZUKI HIROMI , HERMAN JIM
发明人： BAYLIN STEPHEN B , CRIEKINGE WIM VAN , SCHUEBEL KORNEL E , COPE LESLIE , SUZUKI HIROMI , HERMAN JIM
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6827 , C12Q1/6886 , C12Q2600/106 , C12Q2600/154 , C12Q2523/125
摘要： A genome wide microarray gene expression approach for human colorectal cancer cells was used to identify hundreds of hypermethylated genes for colon cancer. We compared isogenic cells altered pharmacologically versus genetically to induce genomic demethylation, to pinpoint genes activated by DNA demethylation, but not by inhibition of class I and II histone deacetylases (HDACs). We achieve an 82% success rate in predicting genes with densely hypermethylated CpG islands and complete gene silencing. The genes are similarly hypermethylated in primary tumors and have previously undetected tumor suppressor functions. The genes can be used diagnostically to detect cancer, pre-cancer, and likelihood of developing cancer.
摘要翻译：用于人结肠直肠癌细胞的全基因组微阵列基因表达方法用于鉴定数百个结肠癌的高甲基化基因。我们比较了等位基因细胞在药理学上与遗传学上的改变，以诱导基因组去甲基化，以确定通过DNA去甲基化激活的基因，但不能抑制I类和II类组蛋白脱乙酰酶（HDAC）。我们在预测密度高的甲基化CpG岛的基因和完整的基因沉默中达到82％的成功率。这些基因在原发性肿瘤中类似地是高甲基化的，并且以前未检测到肿瘤抑制功能。这些基因可以在诊断上用于检测癌症，癌前病症和发展癌症的可能性。

3. 发明申请

WO2006113671A8 METHYLATION MARKERS FOR DIAGNOSIS AND TREATMENT OF CANCERS 审中-公开
标题翻译：用于诊断和治疗癌症的甲基标记物
公开(公告)号：WO2006113671A8
公开(公告)日：2007-06-07
申请号：PCT/US2006014493
申请日：2006-04-17
申请人： ONCOMETHYLOME SCIENCES S A , UNIV JOHNS HOPKINS , CRIEKINGE WIM VAN , STRAUB JOSEF , SIDRANSKY DAVID
发明人： CRIEKINGE WIM VAN , STRAUB JOSEF , SIDRANSKY DAVID
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154
摘要： Two hundred ten markers are provided which are epigenetically silenced in one or more cancer types. The markers can be used diagnostically, prognostically, therapeutically, and for selecting treatments that are well tailored for an individual patient. Restoration of expression of silenced genes can be useful therapeutically, for example, if the silenced gene is a tumor- suppressor gene. Restoration can be accomplished by supplying non-methylated copies of the silenced genes or polynucleotides encoding their encoded products. Alternatively, restoration can be accomplished using chemical demethylating agents or methylation inhibitors. Kits for testing for epigenetic silencing can be used in the context of diagnostics, prognostics, or for selecting "personalized medicine" treatments.
摘要翻译：提供了二百个十个标记物，其在一种或多种癌症类型中被表观遗传沉默。标记物可以在诊断，预后，治疗和选择为个体患者定制的治疗中使用。沉默基因的表达恢复在治疗上是有用的，例如，如果沉默的基因是肿瘤抑制基因。可以通过提供沉默的基因的非甲基化拷贝或编码其编码产物的多核苷酸来实现恢复。或者，可以使用化学去甲基化剂或甲基化抑制剂来实现恢复。用于测试表观遗传学沉默的试剂盒可用于诊断，预后或选择“个性化药物”治疗的上下文中。

4. 发明申请

WO2006113671A3 METHYLATION MARKERS FOR DIAGNOSIS AND TREATMENT OF CANCERS 审中-公开
标题翻译：用于诊断和治疗癌症的甲基标记物
公开(公告)号：WO2006113671A3
公开(公告)日：2009-04-23
申请号：PCT/US2006014493
申请日：2006-04-17
申请人： ONCOMETHYLOME SCIENCES S A , UNIV JOHNS HOPKINS , CRIEKINGE WIM VAN , STRAUB JOSEF , SIDRANSKY DAVID
发明人： CRIEKINGE WIM VAN , STRAUB JOSEF , SIDRANSKY DAVID
IPC分类号： C12Q1/68 , C07H21/02 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154
摘要： Two hundred ten markers are provided which are epigenetically silenced in one or more cancer types. The markers can be used diagnostically, prognostically, therapeutically, and for selecting treatments that are well tailored for an individual patient. Restoration of expression of silenced genes can be useful therapeutically, for example, if the silenced gene is a tumor- suppressor gene. Restoration can be accomplished by supplying non-methylated copies of the silenced genes or polynucleotides encoding their encoded products. Alternatively, restoration can be accomplished using chemical demethylating agents or methylation inhibitors. Kits for testing for epigenetic silencing can be used in the context of diagnostics, prognostics, or for selecting "personalized medicine" treatments.
摘要翻译：提供了二百个十个标记物，其在一种或多种癌症类型中被表观遗传沉默。标记物可以在诊断，预后，治疗和选择为个体患者定制的治疗中使用。沉默基因的表达恢复在治疗上是有用的，例如，如果沉默的基因是肿瘤抑制基因。可以通过提供沉默的基因的非甲基化拷贝或编码其编码产物的多核苷酸来实现恢复。或者，可以使用化学去甲基化剂或甲基化抑制剂来实现恢复。用于测试表观遗传学沉默的试剂盒可用于诊断，预后或选择“个性化药物”治疗的上下文中。

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