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1. 发明申请

WO2006060308A3 HIGH THROUGHPUT METHODS COMPRISING ANALYSIS OF REPETITIVE ELEMENT DNA METHYLATION 审中-公开
标题翻译：包含重复元素DNA甲基化分析的高通量方法
公开(公告)号：WO2006060308A3
公开(公告)日：2007-08-16
申请号：PCT/US2005042885
申请日：2005-11-10
申请人： UNIV SOUTHERN CALIFORNIA , LAIRD PETER W , WEISENBERGER DANIEL J , CAMPAN MIHAELA , LONG TIFFANY I
发明人： LAIRD PETER W , WEISENBERGER DANIEL J , CAMPAN MIHAELA , LONG TIFFANY I
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2561/113 , C12Q2545/114 , C12Q2531/113
摘要： Preferred aspects provide novel high-throughput, sensitive methods (e.g., real-time PCR-based (MethyLight TM ) reactions) for detection and/or measurement of global genomic 5-methylcytosine content, based on measurement of DNA methylation of Alu, LINE-1 repetitive sequences, and the chromosome 1 centromeric satellite alpha and juxtacentromeric satellite 2 repeat sequences. Additional aspects provide sensitive methods for determining the amount of a DNA (e.g., in formalin-fixed, paraffin-embedded tissues). Combined (mean) use of Alu and Sat2 repeat methylation measurements provides for a surprisingly close correlation with global genomic 5-methylcytosine content measurements obtained by HPLC. Methylation of Alu repeats was determined to be closely associated with HPLC-based global methylation levels, as was methylation of satellite 2 and LINE-1 global genomic 5-methylcytosine content. The assays provide surrogate markers for global genomic 5-methylcytosine content analyses, and have substantial utility for high-throughput and population-based studies (e.g., genetic and dietary influences on global DNA methylation, folate deficiency, MTHFR gene polymorphisms, etc).
摘要翻译：优选的方面提供了用于检测和/或测量全局基因组5-甲基胞嘧啶含量的新型高通量，敏感方法（例如，基于实时PCR的（MethyLight TM TM）反应），基于测量 Alu的DNA甲基化，LINE-1重复序列和染色体1着丝粒卫星α和Juxtacentromeric卫星2重复序列。另外的方面提供用于确定DNA量的敏感方法（例如，在福尔马林固定的石蜡包埋的组织中）。 Alu和Sat2重复甲基化测量的组合（平均）使用提供了通过HPLC获得的全球基因组5-甲基胞嘧啶含量测量值的令人惊讶的密切相关性。确定Alu重复的甲基化与基于HPLC的全球甲基化水平密切相关，卫星2和LINE-1全局基因组5-甲基胞嘧啶含量的甲基化也是如此。该测定为全球基因组5-甲基胞嘧啶含量分析提供替代标记，并且对于高通量和基于群体的研究（例如，对全球DNA甲基化，叶酸缺乏，MTHFR基因多态性等的遗传和饮食影响）具有实用性。

2. 发明申请

WO2012167145A2 GENOME-SCALE ANALYSIS OF ABERRANT DNA METHYLATION IN COLORECTAL CANCER 审中-公开
标题翻译：染色体癌细胞DNA甲基化的基因分析
公开(公告)号：WO2012167145A2
公开(公告)日：2012-12-06
申请号：PCT/US2012/040547
申请日：2012-06-01
申请人： UNIVERSITY OF SOUTHERN CALIFORNIA , HINOUE, Toshinori , SHEN, Hui , WEISENBERGER, Daniel J. , LAIRD, Peter W.
发明人： HINOUE, Toshinori , SHEN, Hui , WEISENBERGER, Daniel J. , LAIRD, Peter W.
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/158
摘要： Particular aspects provide methods and compositions (e.g., gene marker panels) having substantial utility for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive DNA methylation-based subgroups of CRC including CpG island methylator phenotype (CIMP) groups (e.g., CIMP-H and CIMP-L) and non-CIMP groups. Exemplary marker panels include: B3GAT2, FOXL2, KCNK13, RAB31 and SLIT1 (CIMP marker panel); and FAM78A, FSTL1, KCNC1, MYOCD, and SLC6A4 (CIMP-H marker panel). Further aspects relate to genetic mutations, and other epigenetic markers relating to said CRC subgroups that can be used in combination with the gene marker panels for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive CIMP and non-CIMP groups.
摘要翻译：特定方面提供方法和组合物（例如，基因标记物组），其具有与基于特异性DNA甲基化的CRC亚基（包括CpG岛）有关的结肠直肠癌（CRC）（例如肿瘤）的诊断，鉴定和分类中的至少一种的实质效用甲基化表型（CIMP）组（如CIMP-H和CIMP-L）和非CIMP组。示例性标记面板包括：B3GAT2，FOXL2，KCNK13，RAB31和SLIT1（CIMP标记物组）; 和FAM78A，FSTL1，KCNC1，MYOCD和SLC6A4（CIMP-H标记物组）。其它方面涉及遗传突变和与所述CRC亚组相关的其它表观遗传标记，其可以与基因标记物组合使用，用于诊断，鉴定和分类结肠直肠癌（CRC）（例如肿瘤）中的至少一种独特的CIMP和非CIMP组。

3. 发明申请

WO2006060308A2 HIGH THROUGHPUT METHODS COMPRISING ANALYSIS OF REPETITIVE ELEMENT DNA METHYLATION 审中-公开
标题翻译：包含重复元素DNA甲基化分析的高通量方法
公开(公告)号：WO2006060308A2
公开(公告)日：2006-06-08
申请号：PCT/US2005/042885
申请日：2005-11-10
申请人： UNIVERSITY OF SOUTHERN CALIFORNIA , LAIRD, Peter, W. , WEISENBERGER, Daniel, J. , CAMPAN, Mihaela , LONG, Tiffany, I.
发明人： LAIRD, Peter, W. , WEISENBERGER, Daniel, J. , CAMPAN, Mihaela , LONG, Tiffany, I.
CPC分类号： C12Q1/6827 , C12Q2561/113 , C12Q2545/114 , C12Q2531/113
摘要： Preferred aspects provide novel high-throughput, sensitive methods (e.g., real-time PCR-based (MethyLight TM ) reactions) for detection and/or measurement of global genomic 5-methylcytosine content, based on measurement of DNA methylation of Alu, LINE-1 repetitive sequences, and the chromosome 1 centromeric satellite alpha and juxtacentromeric satellite 2 repeat sequences. Additional aspects provide sensitive methods for determining the amount of a DNA (e.g., in formalin-fixed, paraffin-embedded tissues). Combined (mean) use of Alu and Sat2 repeat methylation measurements provides for a surprisingly close correlation with global genomic 5-methylcytosine content measurements obtained by HPLC. Methylation of Alu repeats was determined to be closely associated with HPLC-based global methylation levels, as was methylation of satellite 2 and LINE-1 global genomic 5-methylcytosine content. The assays provide surrogate markers for global genomic 5-methylcytosine content analyses, and have substantial utility for high-throughput and population-based studies (e.g., genetic and dietary influences on global DNA methylation, folate deficiency, MTHFR gene polymorphisms, etc).
摘要翻译：优选的方面提供了用于检测和/或测量全局基因组5-甲基胞嘧啶含量的新型高通量，敏感方法（例如，基于实时PCR的（MethyLight TM TM）反应），基于测量 Alu的DNA甲基化，LINE-1重复序列和染色体1着丝粒卫星α和Juxtacentromeric卫星2重复序列。另外的方面提供用于确定DNA量的敏感方法（例如，在福尔马林固定的石蜡包埋的组织中）。 Alu和Sat2重复甲基化测量的组合（平均）使用提供了通过HPLC获得的全球基因组5-甲基胞嘧啶含量测量值的令人惊讶的密切相关性。确定Alu重复的甲基化与基于HPLC的全球甲基化水平密切相关，卫星2和LINE-1全局基因组5-甲基胞嘧啶含量的甲基化也是如此。该测定为全球基因组5-甲基胞嘧啶含量分析提供替代标记，并且对于高通量和基于群体的研究（例如，对全球DNA甲基化，叶酸缺乏，MTHFR基因多态性等的遗传和饮食影响）具有实用性。

4. 发明申请

WO2012167145A3 GENOME-SCALE ANALYSIS OF ABERRANT DNA METHYLATION IN COLORECTAL CANCER 审中-公开
标题翻译：染色体癌细胞DNA甲基化的基因分析
公开(公告)号：WO2012167145A3
公开(公告)日：2013-02-28
申请号：PCT/US2012040547
申请日：2012-06-01
申请人： UNIV SOUTHERN CALIFORNIA , HINOUE TOSHINORI , SHEN HUI , WEISENBERGER DANIEL J , LAIRD PETER W
发明人： HINOUE TOSHINORI , SHEN HUI , WEISENBERGER DANIEL J , LAIRD PETER W
IPC分类号： G01N33/48
CPC分类号： C12Q1/6886 , C12Q2600/154 , C12Q2600/158
摘要： Particular aspects provide methods and compositions (e.g., gene marker panels) having substantial utility for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive DNA methylation-based subgroups of CRC including CpG island methylator phenotype (CIMP) groups (e.g., CIMP-H and CIMP-L) and non-CIMP groups. Exemplary marker panels include: B3GAT2, FOXL2, KCNK13, RAB31 and SLIT1 (CIMP marker panel); and FAM78A, FSTL1, KCNC1, MYOCD, and SLC6A4 (CIMP-H marker panel). Further aspects relate to genetic mutations, and other epigenetic markers relating to said CRC subgroups that can be used in combination with the gene marker panels for at least one of diagnosis, identification and classification of colorectal cancer (CRC) (e.g., tumors) relating to distinctive CIMP and non-CIMP groups.
摘要翻译：特定方面提供方法和组合物（例如，基因标记物组），其具有与基于特异性DNA甲基化的CRC亚基（包括CpG岛）有关的结肠直肠癌（CRC）（例如肿瘤）的诊断，鉴定和分类中的至少一种的实质效用甲基化表型（CIMP）组（如CIMP-H和CIMP-L）和非CIMP组。示例性标记面板包括：B3GAT2，FOXL2，KCNK13，RAB31和SLIT1（CIMP标记物组）; 和FAM78A，FSTL1，KCNC1，MYOCD和SLC6A4（CIMP-H标记物组）。其它方面涉及遗传突变和与所述CRC亚组相关的其它表观遗传标记，其可以与基因标记物组合使用，用于诊断，鉴定和分类结肠直肠癌（CRC）（例如肿瘤）中的至少一种独特的CIMP和非CIMP组。

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